In Some Heavily Pretreated Patients with R/R MM Ide-Cel Continues to Show Deep and Durable Responses – Targeted Oncology

Long-term follow-up data from the KarMMa trial found that treatment with the chimeric antigen receptor (CAR) T-cell therapy, idecabtagene vicleucel (ide-cel; formerly bb2121; Abecma), continues to demonstrate improved survival among heavily pretreated patients with relapsed/refractory multiple myeloma, according to a presentation presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.1

The favorable benefit risk profile of ide-cel, regardless of the number of prior lines of therapy, supports its role as a treatment option for heavily pretreated relapse refractory multiple myeloma, Larry D. Anderson, MD, PhD, associate professor, UT Southwestern Medical Center, said during a presentation of the poster.

At the December 21, 2020, data cutoff, the median follow-up was 24.8 months (range, 1.7-33.6).

Overall response rate (ORR) was 73% in the overall population, including a 33% complete response rate (CRR; complete response [CR] or stringent complete response [sCR]), 20% with a very good partial response (VGPR), and 20% who had a partial response (PR). ORR rates were 50%, 69%, and 81%, respectively, across the 150, 300, and 450 million CAR T cell-dose arms, including CR/sCR rates of 25%, 29%, and 39%.

Of note, ORR did not vary by the number of prior lines of therapy received. For those who received 3 prior lines of therapy (n = 15), the ORR was 73%, including a CRR of 53% and VGPR of 20%, compared with an ORR of 73% in those who received 4 (n = 112) lines of therapy, including a CRR of 30%, VGPR of 23%, and PR of 20%.

Median duration of response (DOR) was 10.9 months (95% CI, 9.0-11.4), including 9.9 months for the 300 million CAR T cells-dose arm and 11.3 months for the 450 million CAR T cells-dose arm -dose arm. Median DOR was 21.5 months in patients who experienced a CR or sCR. Median DOR by response were 21.5 months (95% CI, 12.5 to not estimable [NE]) among those who experienced a CR, 10.4 months (95% CI, 5.1-12.2) for those with VGPR, and 4.5 months (95% CI, 2.9-6.7) in those with PRs.

Moreover, the rate of event-free 24-month DOR appeared to be similar in patients who received 3 or 4 or more lines of therapy. For those who received 3 lines of prior therapy, median DOR was 8.0 months (95% CI, 3.3-11.4), compared with 10.9 months (95% CI, 9.2-13.5) in those who received 4 or more lines of therapy.

Median progression-free survival (PFS) was 8.6 months (95% CI, 5.6-11.6) across all target doses, including 5.8 months for the 300 million CAR T cells-dose arm and 12.2 months for the 450 million CAR T cells-dose arm -dose arm. Similarly, median PFS was similar among those who previously received 3 lines of therapy, compared with 4 or more prior lines of therapy (8.6 months (95% CI, 2.9-12.1) vs 8.9 months (95% CI, 5.4-11.6)]

The median time to first response was 1 month (range, 0.5-8.8), with a median time to CR of 2.8 months (range, 1.0-15.8).

Median overall survival (OS) was 24.8 months (95% CI, 19.9-31.2), including a median OS of 22.0 months (95% CI, 10.-NE) in those who received 3 lines of prior therapy and 25.2 months (95% CI, 19.9-NE) in those who received 4 or more lines of prior therapy. Moreover, OS was 20 months or longer across several key high-risk subgroups, including those aged 65 or older (21.7 months; 95% CI, 17.1-31.2), those with extramedullary disease (20.2 months; 95% CI, 15.5-28.3), and those with triple refractory disease (21.7 months; 95% CI, 18.2-NE).

In regards to safety, cytokine release syndrome (CRS) and neurotoxicity were similar, regardless of prior lines of therapy received, and were mostly low grade. In total, 85% and 18% of the overall population experienced at least 1 CRS or neurotoxicity event, respectively.

The safety profile of ide-cel was consistent with long-term follow-up, with similar rates of infections and secondary primary malignancies, and no unexpected gene therapy related toxicities were observed. The most common grade 3 to 4 adverse events (AEs) in the overall population were neutropenia (89%), anemia (61%), thrombocytopenia (52%), leukopenia (39%), lymphopenia (27%), and infections (27%).

Long-term results from the KarMMA trial continue to demonstrate frequent, deep, and durable responses in heavily pretreated patients with [relapsed/refractory multiple myeloma], the study authors write in the poster. ORR, CRR, DOR, and PFS were consistent with previous reports and patients received similar benefit regardless of the number of prior lines of therapy.

In his presentation, Anderson presented data on long-term efficacy and safety following treatment with ide-cel in the pivotal phase 2 KarMMa trial (NCT03361748)-including overall data and by prior line of therapy that patients had received (3 vs 4), since the FDA label is requiring at least 4 prior lines, and this study only required 3, he added.

In total, 140 patients who had received at least 3 prior lines of therapy for multiple myeloma including an IMiD, a PI, and an anti-CD38 antibody and were refractory to their last treatment regimen, were enrolled in the study. However, only 128 patients received infusion with ide-cel.

Patients were treated with ide-cel across the target dose range of 150 (n = 4), 300 (n = 70), and 450 (n = 54) million CAR T cells.

ORR served as the primary end point of the study. Secondary end points included CRR, safety, DOR, PFS, OS, pharmacokinetics, minimal residual disease, quality of life, and health economics and outcomes research.

At baseline, the median patient age was 61 years (range, 33-78) and patients had a median of 6 years (range, 1-18) since their diagnosis. A majority of the patients were male (59%), had high tumor burden (51%), B-cell maturation antigen (BCMA) expression 50% at screening (85%), ECOG performance status of 1 (53%), and Revised International Staging System disease stage of II (70%). Thirty-five percent of patients had high-risk features.2

The median number of prior therapies was 6 (range, 3-16) and 94% had previously undergone at least 1 autologous hematopoietic stem cell transplant (94%). Eighty-eight percent of patients required bridging therapy. Eighty-nine percent of patients had double-refractory disease, 84% were triple-refractory, and 26% were penta-refractory.

Patients who had received 3 prior lines of therapy had similar baseline characteristics, compared with those who received 4 prior lines, including differences in extramedullary disease, high-risk cytogenetics, prior refractoriness, and time since the initial diagnosis to screening.

Patients with relapsed/refractory multiple myeloma previously exposed to immunomodulatory agents, protease inhibitors, and anti-CD38 antibodies have poor outcomes with subsequent therapy using previously approved regimens, with expected response rates in the 26% to 31% range, PFS in the 2- to 4-month range, and overall survival less than 9 months, Anderson explained.

However, the BCMA-directed CAR T-cell therapy previously demonstrated favorable tolerability with deep, durable responses in patients who were heavily pretreated with relapsed/refractory multiple myeloma.2 As a result, the FDA approved the agent for the treatment of adult patients with relapsed or refractory multiple myeloma after 4 or more prior therapies, including an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody, representing the first BCMAdirected CAR T-cell therapy approved.3

The study authors noted that ide-cel is being explored in ongoing clinical trials, including the following:

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In Some Heavily Pretreated Patients with R/R MM Ide-Cel Continues to Show Deep and Durable Responses - Targeted Oncology

Karen Hasty Named Among 2021 Super Women In Business by Memphis Business Journal – UTHSC News

Karen Hasty, PhD, a professor, researcher, and director of Basic Research in the Department of Orthopaedic Surgery and Biomedical Engineering/Campbell Clinic in the College of Medicine at the University of Tennessee Health Science Center, has been named among the 2021 Super Women in Business by the Memphis Business Journal. The annual list honors women business leaders for their career accomplishments and work in the Memphis community.

I am thrilled to receive this honor, said Dr. Hasty, who holds the George Thomas Wilhelm Endowed Professorship in Orthopaedic Surgery. It allows me to have a new platform to bring attention to many philanthropic projects, while continuing to encourage young women to consider medical careers in orthopaedic surgery or in academia.

Dr. Hastys philanthropic efforts include establishing a summer internship for undergraduate women called the Kappa Delta Foundation Orthopaedic Research Internship, which encourages them to consider orthopaedic surgery as a career option. It provides stipends, housing, and research funding for selected participants. She has also served as the medical chair for the West Tennessee Board of the Arthritis Foundation since 2017.

Because of her professional appointment, Dr. Hasty holds a dual position with UTHSC and the Memphis VA Medical Center, where she does basic science research. Studying arthritis for more than four decades, her current studies focus on exploring new therapies to interrupt the disease progression and stimulate repair of joint destruction. Dr. Hastys research efforts have been funded by the VA, the National Institutes of Health, the Department of Defense, and the Arthritis Foundation.

She is currently in a research collaboration with Revotek Co., Ltd., in the Memphis Institute of Regenerative Medicine (MIRM). The project titled, MIRM Project 3: Stem Cell-Enhanced Tissue Regeneration: Engineering of Vascularized Bone/Cartilage Graft from Adipose-Derived Stem Cells, will utilize Revoteks cell encapsulation technology of Biosynspheres and bioprinting for basic and translational research in stem cell regenerative medicine.

Dr. Hasty earned her Bachelor of Science degree in microbiology from the University of Tennessee, Knoxville and received her MS and PhD degrees in anatomy from UTHSC. She began working at the university in 1977, after a stint at Boston Childrens Hospital, where she studied hemoglobin A1c, a marker that determines long-term control of blood glucose in diabetes.

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High Overall Response Rates Achieved With Cirmtuzumab/Ibrutinib in MCL and CLL – Targeted Oncology

The combination of cirmtuzumab and ibrutinib (Imbruvica) achieved high overall response rates (ORR) in patients with mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL) who were treated in a phase 1/2 study, according to findings from presented during the 2021 ASCO Annual Meeting.

The safety profile of the treatment regimen was also well tolerated, Hun Ju Lee, MD stated during the presentation.

The majority of the patients demonstrated a significant reduction in tumor sizes, lead study author Lee, assistant professor of medicine in the Department of Lymphoma & Myeloma at The University of Texas MD Anderson Cancer Center said during the presentation.

ORR for patients with MCL was 83.3% and was 91.1% for patients with CLL. The complete response rates were 38.9% and 14.7% for the MCL and CLL arms, respectively. Ultimately, 94.4% of patients with MCL and 100% of patients with CLL elicited a clinical benefit from the cirtuzumab/ibrutinib regimen.

The median progression free survival in both cancers was not reached.

Because MCL and CLL are considered incurable, the study aimed to test the efficacy and safety profile of cirmtuzumab, which inhibits tumor promoting activity of onco-embryonic tyrosine kinase receptor ROR1 found in many solid and hematologic cancers, plus ibrutinib in patients with relapsed/refractory MCL or treatment nave or relapsed/refractory CLL.

The study was performed in 3 parts with separate arms. Part 1, for dose escalation; part 2, for dose expansion; and part 3, comparing cirmtuzumab plus ibrutinib with ibrutinib alone in CLL.

Overall, 26 patients with refractory MCL (median age 66.5, 15.4% women) and 34 patients with treatment nave or RR CLL (median age 68, 23.5% women) were enrolled in the study.

For part 1, 12 patients with MCL were enrolled, and 5 into part 2. The median number of prior regimens was 2, including patients relapsing after ibrutinib (n=4), autologous stem-cell transplantation (n=3), autologous stem cell transplantation/allogenic stem cell transplantation (1) and autologous stem cell transplantation /CAR-T (1). For patients with CLL, at least 74% were high risk, as determined by unmutated IGHV, del17p and/or del11q, in parts 1 and 2.

In part 1, cirmtuzumab was given intravenously 5 times every 2 weeks, and then every 4 weeks, at 2 to 16 mg. Three-hundred or 600 mg doses were also examined. Researchers assessed the safety profile of cirmtuzumab during the first 28 days, which was then followed by ibrutinib at approved doses for each indication. A treatment regimen of cirmtuzumab (600 mg) given intravenously 3 times every 2 weeks, and then every 4 weeks, in combination with ibrutinib starting day 0, was chosen as the recommended dosing for parts 2 and 3.

In summary, cirmtuzumab plus ibrutinib is a very well tolerated regimen, Lee noted.

Adverse events with 20% or greater incidence were recorded, including fatigue (n=11), diarrhea (n=9), contusion (n=7), dizziness (n=7) and nausea (n=7). The efficacy is robust in many of these pre-treated patients, [including] high response, rate durable response [and] encouraging PFS, demonstrating clinical benefit, he concluded.

Of note, the phase 2 study for CLL is completed, and is awaiting a long-term follow-up. Phase 2 for MCL is currently enrolling.

References

Lee HJ, Choi M, Siddiqi T, et al. Phase 1/2 study of cirmtuzumab and ibrutinib in mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL).J Clin Oncol. 2021;39(suppl 15; abstr 7556).

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Chao family gifts to UCI Health for cancer care top $50 million – UCI News

Orange, Calif., June 1, 2021 With its current gift, longtime UCI Health benefactor the Chao family has committed $50 million since 1995 to UCI Health toward advancing cancer care in Orange County and beyond. The familys latest gift will name the cancer center at the new UCI Medical Center in Irvine, expanding access to leading-edge cancer treatments and therapies, promising clinical trials, and world-class cancer care driven by the latest in precision medicine.

Few families have been as generous in support of their fellow residents of Orange County as the Chao family, said Chancellor Howard Gillman. This latest extraordinary gift is testament to their belief in the power of academic medicine to lead the fight against cancer and to provide the best and most up-to-date care to cancer patients.

The Chao Family Comprehensive Cancer Center and Ambulatory Care will be one of three medical facilities at the new $1.2 billion medical center adjacent to the UCI campus; the others are a 144-bed acute care hospital with an emergency department and the Center for Advanced Care. The cancer care center is strategically located at the new medical center campus in Irvine to allow patients to receive multidisciplinary care by interprofessional and integrative teams working together to apply the latest innovations from university-backed clinical research.

The Chao familys commitment to UCI and the fight against cancer has brought much-needed hope to patients and their families over the past 25 years, said Steve A.N. Goldstein, M.A., M.D., Ph.D., FAAP, UCI vice chancellor for health affairs. Their most recent gift extends the opportunity for cancer patients to receive lifesaving therapies and empowers the worlds top cancer clinician-scientists to advance cancer treatment through personalized healthcare. This is only possible at an academic health center committed to developing and applying advanced AI, machine-learning, genomics and therapeutics to clinical practice.

More than anyone else, the Chao familys generosity and dedication has changed the face of cancer care and research in Orange County, said Richard Van Etten, M.D., Ph.D., director of UCIs Chao Family Comprehensive Cancer Center in Orange, the only National Cancer Institute-designated comprehensive cancer center based in Orange County. The Chao familys investment allows UCI Health to treat the most complex cancers, and patients benefit from the power of the University of California Cancer Consortium.

Since their first gift to the university in 1995, three generations of Chaos have supported the growth of UCIs cancer program, including expanded clinical care and advanced research facilities and the creation last year of Orange Countys only adult hematopoietic stem cell/bone marrow transplant program. Today, UCIs Chao Family Comprehensive Cancer Center in Orange is one of only 51 NCI-designated centers across the U.S. those that meet the highest standards for an institutions commitment to and excellence in cancer research and clinical care.

Doing good in our community has always been very important to our family, said Allen Chao. We are proud to continue our partnership with UCI and to know that community members from all walks of life benefit from the lifesaving treatments offered here.

Its a value passed down to us from our matriarch and patriarch, Hsu Hwa Chao and Hsi Hsiung Chao, he said.

In 1999, Allen Chao developed stomach cancer. He sought the care of UCI Health gastroenterologistDr. Kenneth Chang, who helped to remove all signs of the disease. Chang, head of gastrointestinal oncology, also directs UCIs Chao Family Comprehensive Digestive Disease Center (CDDC), supported by the Chao family as part of its vision to expand access to cancer care.

The CDDC is a multidisciplinary center where gastroenterologists, hepatologists, oncologists, surgeons and other specialists work in concert to provide the best care for the most complex digestive diseases, including cancer of the colon, liver, stomach, esophagus and pancreas. Under Changs leadership and with the support of the Chao family, the CDDC has become a leader in innovation and clinical care, advancing research and clinical trials on the development of treatments for digestive cancers. Chang has pioneered the development of endoscopic ultrasound guided fine-needle aspiration and injection, techniques that have revolutionized the intervention and treatment of many gastrointestinal diseases and cancers.

The Chao family has expanded access to the most innovative treatments for those with cancer and those with gastrointestinal diseases, which are also highly prevalent among the Asian population, Chang said.

The Chao familys commitment is a key to extending access to UCI Health cancer care and clinical trials to residents across the region. The new cancer center and hospital are slated to begin construction later this year and open in late 2023 and 2025, respectively, according to UCI Health CEO Chad Lefteris.

We encourage others to do good in their community in whatever way they can, Chao said. Philanthropy can take many forms and is not limited to financial support.

I commend the Chao family for their naming gift to the Comprehensive Cancer Center and Ambulatory Care facility at the UCI Medical Center in Irvine, and we are grateful for UCIs continued partnership and contributions to maintaining the wellbeing of Irvine, said Irvine Mayor Farrah Khan. This new facility will provide the world-class cancer research and care that befits the unsurpassed quality of life for Irvine residents by providing additional healthcare options and new jobs for the community.

Orange Countys landmark cancer center

Established in 1989 as Orange Countys first cancer center, the UCI facility in Orange achieved its initial National Cancer Institute cancer center designation in 1994 and comprehensive designation in 1997. The familys landmark 1995 gift catalyzed the universitys efforts to earn this status.

The significance for Orange County was profound. A region with a population greater than that of 20 states now had an institution where people with advanced-stage or treatment-resistant diseases could receive world-class cancer care advanced by basic and translational research, including access to early-phase clinical trials involving the very latest therapies.

A strong research base, in particular, helps drive progress, Van Etten said. It is our mission to translate the findings of basic research into treatments that can benefit patients. Institutions lacking their own research base can follow and adopt advances developed elsewhere, but they cannot lead in the same way comprehensive cancer centers that integrate research with clinical care can.

The current gift furthers UCI efforts to expand cancer prevention and screening, address disparities and provide equitable access to specialty cancer care. For example, enrollment in potentially lifesaving clinical trials increased by more than 260 percent between 2015 and 2020.

UCIs advancements in cancer care are made possible thanks to the Chao familys friendship and support, and we are excited to be able to offer this level of care across Orange County, Lefteris said. In just the last five years, the UCI Chao Family Comprehensive Cancer Center in Orange and our community locations across Orange County have seen more than 400,000 patient visits.

David Liu is one of the people whose lives were saved by UCI Health cancer specialists supported by the Chao family. Diagnosed with stage 3 colon cancer a decade ago at a community hospital, the Orange County resident turned to the regions only academic health system for treatment.

This is a wonderful organization, and I was treated by many excellent doctors, nurses and other staff, said Liu, an engineer and part-time musician whose band supports fundraisers for several community groups. It really touches me that the Chao family has committed to a vision of a cancer center available for everybody.

About the UCI Health: UCI Healthis the clinical enterprise of the University of California, Irvine. Patients can access UCI Health at primary and specialty care offices across Orange County and at its main campus,UCI Medical Center in Orange, Calif. The 418-bed acute-care hospital, listed among Americas Best Hospitals byU.S. News & World Reportfor 20 consecutive years, provides tertiary and quaternary care, ambulatory and specialty medical clinics, as well as behavioral health and rehabilitation services. UCI Medical Center is home to Orange Countys onlyNational Cancer Institute-designated comprehensive cancer center,high-risk perinatal/neonatal programandAmerican College of Surgeons-verified Level I adult and Level II pediatric trauma centerandregional burn center. It is the primary teaching hospital for theUCI School of Medicine. UCI Health serves a region of nearly 4 million people in Orange County, western Riverside County and southeast Los Angeles County. Follow us onFacebookandTwitter.

About the University of California, Irvine: Founded in 1965, UCI is the youngest member of the prestigious Association of American Universities and is ranked among the nations top 10 public universities by U.S. News & World Report. The campus has produced three Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UCI has more than 36,000 students and offers 224 degree programs. Its located in one of the worlds safest and most economically vibrant communities and is Orange Countys second-largest employer, contributing $7 billion annually to the local economy and $8 billion statewide. For more on UCI, visit http://www.uci.edu.

About UCIs Brilliant Future campaign:Publicly launched on Oct. 4, 2019, the Brilliant Future campaign aims to raise awareness and support for UCI. By engaging 75,000 alumni and garnering $2 billion in philanthropic investment, UCI seeks to reach new heights of excellence instudent success, health and wellness, research and more. Learn more by visitingbrilliantfuture.uci.edu.

Media access: Radio programs/stations may, for a fee, use an on-campus ISDN line to interview UCI faculty and experts, subject to availability and university approval. For more UCI news, visit news.uci.edu. Additional resources for journalists may be found at communications.uci.edu/for-journalists.

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Chao family gifts to UCI Health for cancer care top $50 million - UCI News

New Data on KEYTRUDA (pembrolizumab) Plus LENVIMA (lenvatinib) Versus Sunitinib in First-Line Treatment for Patients With Advanced Renal Cell…

KENILWORTH, N.J., & WOODCLIFF LAKE, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside the United States and Canada, and Eisai Inc. today announced new investigational data from the pivotal Phase 3 CLEAR (Study 307)/KEYNOTE-581 trial, which evaluated the combinations of KEYTRUDA, Mercks anti-PD-1 therapy, plus LENVIMA, the orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai, and LENVIMA plus everolimus versus sunitinib for the first-line treatment of patients with advanced renal cell carcinoma (RCC). Results from a new analysis evaluating health-related quality of life (HRQoL) based on patient-reported outcomes are being presented during an oral abstract session at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #4502). Data from CLEAR/KEYTNOTE-581 were originally presented at the 2021 Genitourinary Cancers Symposium (ASCO GU) and published in the New England Journal of Medicine, and data from this trial are currently under review with the U.S. Food and Drug Administration (FDA).

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20210607005121/en/

This new analysis expands our understanding of the results weve seen from the CLEAR/KEYNOTE-581 trial in the treatment of patients with advanced renal cell carcinoma, said Dr. Robert Motzer, Medical Oncologist, Kidney Cancer Section Head, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center. The additional data showed an improvement of specific health-related quality of life measures for patients who received KEYTRUDA plus LENVIMA compared with sunitinib, supporting the importance of this combination as a potential new first-line treatment option for patients.

We continue to see an increasing number of patients diagnosed with advanced renal cell carcinoma and remain committed to improving outcomes for those facing this difficult-to-treat disease, said Dr. Gregory Lubiniecki, Vice President, Oncology Clinical Research, Merck Research Laboratories. This new analysis builds on earlier findings from the CLEAR/KEYNOTE-581 trial and further supports the potential use of KEYTRUDA plus LENVIMA for the treatment of patients in the first-line setting.

This analysis addresses questions of interest to healthcare professionals who treat patients with advanced renal cell carcinoma and reinforces the KEYTRUDA plus LENVIMA combination as a possible new treatment option for patients with this disease, said Dr. Takashi Owa, Chief Medicine Creation Officer and Chief Discovery Officer, Oncology Business Group at Eisai. These results reflect Eisai and Mercks shared commitment to relentlessly pursue thorough scientific investigations with the goal of improving cancer care.

Data From HealthRelated Quality of Life (HRQoL) Analysis From CLEAR/KEYNOTE-581

In an analysis of a secondary endpoint of HRQoL scores in the CLEAR/KEYNOTE-581 trial, KEYTRUDA plus LENVIMA and LENVIMA plus everolimus were evaluated to determine the impact on HRQoL compared to sunitinib in patients with advanced RCC. This was assessed based on patient-reported outcomes using three HRQoL and symptom measures: Functional Assessment of Cancer Therapy Kidney Symptom Index Disease-Related Symptoms (FKSI-DRS), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer Core 30 (EORTC QLQ-C30) and European Quality of Life Five-Dimensions 3-Level System (EuroQoL EQ-5D-3L). Unless otherwise noted, HRQoL analyses were based on data from randomized patients who received at least one dose of study treatment. No adjustments for multiple testing or estimation were used; p-values (two-sided) and confidence intervals (CI) are nominal and descriptive. Longitudinal change from baseline was assessed by mixed model analysis. Least squares mean differences (LSMD) and 95% CI were calculated from baseline. Time to deterioration (based on changes in HRQoL and disease-related symptom scores meaningful thresholds) was assessed using time to first deterioration (TTD), which is the number of weeks between randomization and the first deterioration event, and time until definitive deterioration (TUDD), which is the number of weeks between randomization and the earliest deterioration event with no subsequent recovery above the deterioration threshold or no subsequent HRQoL assessment data. All times to deterioration were calculated and compared using the Kaplan-Meier method, stratified log-rank tests and Cox models.

KEYTRUDA plus LENVIMA demonstrated similar changes from baseline at mean follow-up (Week 46) on 14 out of 18 HRQoL and disease-related symptom scores and better HRQoL and disease-related symptom scores for the following measures (LSMD [95% CI]): physical functioning (3.01 [0.48, 5.54]), fatigue (-2.80 [-5.52, -0.08]), dyspnea (-2.79 [-5.33, -0.25]) and constipation (-2.19 [-4.19, -0.18]), as measured by the QLQ-C30, versus sunitinib. LENVIMA plus everolimus demonstrated similar changes from baseline at mean follow-up (Week 46) on 14 out of 18 HRQoL and disease-related symptom scores and worse HRQoL and disease-related symptom scores in the following measures (LSMD [95% CI]): Global Health Score/QoL (-2.81 [-5.08, -0.54]), pain (2.80 [0.11, 5.49]), appetite loss (4.23 [1.34, 7.13]) and diarrhea (5.26 [2.61, 7.91]) compared to sunitinib.

KEYTRUDA plus LENVIMA demonstrated a similar TTD in 14 out of 18 HRQoL and disease-related symptom scores, and a delay in TTD for physical functioning, dyspnea, appetite loss, and EQ-5D visual analog scale compared to sunitinib. KEYTRUDA plus LENVIMA demonstrated a delay in TUDD in 16 out of 18 HRQoL and disease-related symptom scores and a similar TUDD for cognitive functioning and financial difficulties compared to sunitinib.

Dr. Motzer has provided consulting and advisory services for Merck and Eisai.

About CLEAR (Study 307)/KEYNOTE-581

The CLEAR/KEYNOTE-581 trial is a multicenter, randomized, open-label, Phase 3 trial (ClinicalTrials.gov, NCT02811861) evaluating LENVIMA in combination with KEYTRUDA or in combination with everolimus versus sunitinib for the first-line treatment of patients with advanced RCC. The primary endpoint is progression-free survival, as assessed by independent review per RECIST v1.1. Secondary endpoints include overall survival, objective response rate, HRQoL and safety. A total of 1,069 patients were randomized (1:1:1) to receive:

Treatment continued until unacceptable toxicity or disease progression as determined by the investigator and confirmed by independent radiologic review committee using RECIST v1.1. Administration of KEYTRUDA plus LENVIMA was permitted beyond RECIST-defined disease progression if the patient was clinically stable and considered by the investigator to be deriving clinical benefit. KEYTRUDA was continued for a maximum of 24 months; however, treatment with LENVIMA could be continued beyond 24 months. Assessment of tumor status was performed at baseline and then every eight weeks.

About Renal Cell Carcinoma (RCC)

Worldwide, it is estimated there were more than 431,000 new cases of kidney cancer diagnosed and more than 179,000 deaths from the disease in 2020. In the U.S., it is estimated there will be nearly 76,000 new cases of kidney cancer diagnosed and almost 14,000 deaths from the disease in 2021. Renal cell carcinoma is by far the most common type of kidney cancer; about nine out of 10 kidney cancer diagnoses are RCC. Renal cell carcinoma is about twice as common in men as in women. Most cases of RCC are discovered incidentally during imaging tests for other abdominal diseases. Approximately 30% of patients with RCC will have metastatic disease at diagnosis, and as many as 40% will develop metastases after primary surgical treatment for localized RCC. Survival is highly dependent on the stage at diagnosis, and the five-year survival rate is 13% for patients with metastatic disease.

About KEYTRUDA (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industrys largest immuno-oncology clinical research program. There are currently more than 1,400 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications in the U.S.

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) 1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (CPS 10), as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

KEYTRUDA is indicated for the first-line treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Cancer

KEYTRUDA, in combination with trastuzumab, and fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Endometrial Carcinoma

KEYTRUDA, in combination with LENVIMA, is indicated for the treatment of patients with advanced endometrial carcinoma that is not MSI-H or dMMR, who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial.

Tumor Mutational Burden-High

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation.

Triple-Negative Breast Cancer

KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Selected Important Safety Information for KEYTRUDA

Severe and Fatal Immune-Mediated Adverse Reactions

KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or the programmed death ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of antiPD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.

Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% of these patients interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%) reactions. Systemic corticosteroids were required in 69% (33/48); additional immunosuppressant therapy was required in 4.2% of patients. Colitis led to permanent discontinuation of KEYTRUDA in 0.5% (15) and withholding in 0.5% (13) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Colitis resolved in 85% of the 48 patients.

Hepatotoxicity and Immune-Mediated Hepatitis

KEYTRUDA as a Single Agent

KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 68% (13/19) of patients; additional immunosuppressant therapy was required in 11% of patients. Hepatitis led to permanent discontinuation of KEYTRUDA in 0.2% (6) and withholding in 0.3% (9) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Hepatitis resolved in 79% of the 19 patients.

KEYTRUDA with Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST) (13%) were seen, which was at a higher frequency compared to KEYTRUDA alone. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. In patients with ALT 3 times upper limit of normal (ULN) (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients who were rechallenged with either KEYTRUDA (n=3) or axitinib (n=34) administered as a single agent or with both (n=55), recurrence of ALT 3 times ULN was observed in 1 patient receiving KEYTRUDA, 16 patients receiving axitinib, and 24 patients receiving both. All patients with a recurrence of ALT 3 ULN subsequently recovered from the event.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or higher, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold KEYTRUDA depending on severity. Adrenal insufficiency occurred in 0.8% (22/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.3%) reactions. Systemic corticosteroids were required in 77% (17/22) of patients; of these, the majority remained on systemic corticosteroids. Adrenal insufficiency led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.3% (8) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Hypophysitis

KEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Hypophysitis occurred in 0.6% (17/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.2%) reactions. Systemic corticosteroids were required in 94% (16/17) of patients; of these, the majority remained on systemic corticosteroids. Hypophysitis led to permanent discontinuation of KEYTRUDA in 0.1% (4) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Thyroid Disorders

KEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Thyroiditis occurred in 0.6% (16/2799) of patients receiving KEYTRUDA, including Grade 2 (0.3%). None discontinued, but KEYTRUDA was withheld in <0.1% (1) of patients.

Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent discontinuation of KEYTRUDA in <0.1% (2) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. Hypothyroidism occurred in 8% (237/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (6.2%). It led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.5% (14) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. The majority of patients with hypothyroidism required long-term thyroid hormone replacement. The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC, occurring in 16% of patients receiving KEYTRUDA as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in 389 adult patients with cHL (17%) receiving KEYTRUDA as a single agent, including Grade 1 (6.2%) and Grade 2 (10.8%) hypothyroidism.

Type 1 Diabetes Mellitus (DM), Which Can Present With Diabetic Ketoacidosis

Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold KEYTRUDA depending on severity. Type 1 DM occurred in 0.2% (6/2799) of patients receiving KEYTRUDA. It led to permanent discontinuation in <0.1% (1) and withholding of KEYTRUDA in <0.1% (1). All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Immune-Mediated Nephritis With Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.1%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 89% (8/9) of patients. Nephritis led to permanent discontinuation of KEYTRUDA in 0.1% (3) and withholding in 0.1% (3) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Nephritis resolved in 56% of the 9 patients.

Immune-Mediated Dermatologic Adverse Reactions

KEYTRUDA can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with antiPD-1/PD-L1 treatments. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes. Withhold or permanently discontinue KEYTRUDA depending on severity. Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of patients receiving KEYTRUDA, including Grade 3 (1%) and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 40% (15/38) of patients. These reactions led to permanent discontinuation in 0.1% (2) and withholding of KEYTRUDA in 0.6% (16) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 6% had recurrence. The reactions resolved in 79% of the 38 patients.

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received KEYTRUDA or were reported with the use of other antiPD-1/PD-L1 treatments. Severe or fatal cases have been reported for some of these adverse reactions. Cardiac/Vascular: Myocarditis, pericarditis, vasculitis; Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barr syndrome, nerve paresis, autoimmune neuropathy; Ocular: Uveitis, iritis and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; Gastrointestinal: Pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitis; Musculoskeletal and Connective Tissue: Myositis/polymyositis rhabdomyolysis (and associated sequelae, including renal failure), arthritis (1.5%), polymyalgia rheumatica; Endocrine: Hypoparathyroidism; Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% of 2799 patients receiving KEYTRUDA. Monitor for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion for Grade 1 or Grade 2 reactions. For Grade 3 or Grade 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

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New Data on KEYTRUDA (pembrolizumab) Plus LENVIMA (lenvatinib) Versus Sunitinib in First-Line Treatment for Patients With Advanced Renal Cell...

Sorrento and Researchers at Karolinska Institutet Have Signed a Research Collaboration Agreement on iPSC-Derived Dimeric – GlobeNewswire

SAN DIEGOandSTOCKHOLM, Sweden, June 04, 2021 (GLOBE NEWSWIRE) -- Sorrento Therapeutics, Inc. (Nasdaq: SRNE, "Sorrento")today announced that the Company has entered into an additional collaborative agreement with NextGenNK Competence Center-associated research groups at the Department of Medicine, Huddinge, KarolinskaInstitutet(KI) inStockholm, Sweden, aimed at producing novelcell-based therapeutics using natural killer (NK) cells derived from induced pluripotent stem cells (iPSCs). Sorrento and KI are collaborative partners in the Competence Center for the development of next-generation NK cell-based cancer immunotherapies (NextGenNK) coordinated by KI.

Under the agreement, Sorrento willprovide know-how in the core chimeric antigen receptor (CAR) and dimeric antigen receptor (DAR) technologies and support the collaborative effort to develop newCAR-NK andDAR-NK candidates, as well as fund the translational validation of the technologies. Multiple product candidates will be developed and tested in the initial phase of the planned work, with the goal that the candidate products will qualify for further human clinical trials.

The foundational Sorrento research assets critical to this program are novel proprietary CAR and DARconstructsidentified through Sorrentos proprietary G-MAB fully human antibody library and previously validated as determinants of cell-based therapy potency against hematologic and solid tumors.

It is a privilege to continue and extend ourcollaborative workwith the distinguished KI faculty. We are proud to contribute our technologiesto producenewoptimizedoff-the-shelf adoptive NK cell immunotherapies," said Dr.Henry Ji, Chairman and CEO of Sorrento. "Our partnership with KIcombines our know-how with the expertise of aworld-renownedinstitution in thefield ofNK cell therapy.Thesetypes ofpartnershipsareessential inadvancing medicine and bringingnew solutionstocancerpatients inneed.

KI scientists within NextGenNK will establishiPSC-derived NK-basedtherapeutic candidatesutilizing Sorrentos constructs and DAR technology. Work within KI has contributed to the development of methodologies that consistently generate robust and potent NK cell lineages following iPSC differentiation. Clinical trials of NK cell-based therapies for treatment of multiple myeloma led by researchers at KI have yielded promising preliminary results with long-lasting remissions. In a very cross-knit collaboration between Sorrento and KI, the team will aim to establish novel allogeneic, off-the-shelf, retargeted NK cell-based therapies.

Utilizing iPSCs enables mass production of off-the-shelf NK cell therapies that leverage Sorrentos existing manufacturing infrastructure and know-how. Sorrento expects these validated re-engineered NK cell-based therapeutic candidates could potentially become a new generation in off-the-shelf treatments for cancer and infectious diseases. Thecoreresearch will be performed atKarolinskaInstitutet withactiveinvolvement oftheSorrento R&Dteamin San Diego.

The present collaboration brings together key competence from Sorrento and KI in an important area of cancer immunotherapy research. Sorrentos intellectual contribution to the research at the Competence Center is a critical piece in enabling retargeted off-the-shelf NK cell products, said Evren Alici, Principal Investigator at KI.

This is an important step in further enabling academic and industrial partnerships in the mission of achieving common goals for advancement of novel cancer immunotherapies, said Hans-Gustaf Ljunggren, Director of the NextGenNK Competence Center.

About Sorrento Therapeutics, Inc.

Sorrento is a clinical stage, antibody-centric, biopharmaceutical company developing new therapies to treat cancers and COVID-19. Sorrento's multimodal, multipronged approach to fighting cancer is made possible by its extensive immuno-oncology platforms, including key assets such as fully human antibodies (G-MAB library), clinical stage immuno-cellular therapies (CAR-T, DAR-T), antibody-drug conjugates (ADCs), and clinical stage oncolytic virus (Seprehvir). Sorrento is also developing potential antiviral therapies and vaccines against coronaviruses, including COVIGUARD, COVI-AMG, COVISHIELD, Gene-MAb, COVI-MSC and COVIDROPS; and diagnostic test solutions, including COVITRACK, COVISTIX and COVITRACE.

Sorrento's commitment to life-enhancing therapies for patients is also demonstrated by our effort to advance a first-in-class (TRPV1 agonist) non-opioid pain management small molecule,resiniferatoxin(RTX), and SP-102 (10 mg, dexamethasone sodium phosphate viscous gel) (SEMDEXA), a novel, viscous gel formulation of a widely used corticosteroid for epidural injections to treat lumbosacral radicular pain, or sciatica, and to commercializeZTlido (lidocaine topical system) 1.8% for the treatment of post-herpetic neuralgia. RTX has completed a Phase IB trial for intractable pain associated with cancer and a Phase 1B trial in osteoarthritis patients. SEMDEXA is in a pivotal Phase 3 trial for the treatment of lumbosacral radicular pain, or sciatica.ZTlido was approved by the FDA on February 28, 2018.

For more information, visit http://www.sorrentotherapeutics.com.

About KarolinskaInstitutet

Karolinska Institutet is one of the worlds leading medical universities. Our vision is to advance knowledge about life and strive towards better health for all. Karolinska Institutet accounts for the single largest share of all academic medical research conducted in Sweden and offers the countrys broadest range of education in medicine and health sciences. The Nobel Assembly at Karolinska Institutet selects the Nobel laureates in Physiology or Medicine.

For more information about KarolinskaInstitutet, visit https://ki.se/en/research/research-at-karolinska-institutet.

For more information about NextGenNK, visit https://ki.se/en/research/nextgennk.

Forward-Looking Statements

This press release and any statements made for and during any presentation or meeting contain forward-looking statements related to Sorrento Therapeutics, Inc., under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995 and subject to risks and uncertainties that could cause actual results to differ materially from those projected. Forward-looking statements include statements regarding Sorrentos and KIs to bring off-the-shelf NK cell-based cancer treatments to patients; Sorrentos and KIs ability to produce novel cell-based therapeutics using NK cells derived from iPSCs; Sorrentos and KIs ability to develop new CAR-NK and DAR-NK candidates and to validate such technologies; the expectation that the collaborative effort will result in the development and testing of multiple product candidates and that any such product candidates will qualify for human clinical trials; the ability of KI scientists to establish iPSC-derived NK-based therapeutic candidates utilizing Sorrentos constructs and DAR technology; the expectation that utilizing iPSCs will enable mass production of off-the-shelf NK cell therapies; the potential for Sorrento to be able to use its existing manufacturing infrastructure and know-how to mass produce any off-the-shelf NK cell therapies; the potential for re-engineered NK cell-based therapeutic candidates to become a new generation in off-the-shelf treatments for cancer and infectious diseases; and the therapeutic potential of iPSC-derived NK-based therapeutic candidates. Risks and uncertainties that could cause our actual results to differ materially and adversely from those expressed in our forward-looking statements, include, but are not limited to: risks related to Sorrento's and its subsidiaries, affiliates and partners technologies and prospects and collaborations with partners, including, but not limited to: risks related to seeking regulatory approvals; clinical development risks, including risks in the progress, timing, cost, and results of clinical trials and product development programs; risk of difficulties or delays in obtaining regulatory approvals; risks that clinical study results may not meet any or all endpoints of a clinical study and that any data generated from such studies may not support a regulatory submission or approval; risks that prior test, study and trial results may not be replicated in future studies and trials; risks of manufacturing and supplying drug product; risks related to leveraging the expertise of its employees, subsidiaries, affiliates and partners to assist Sorrento in the execution of its therapeutic antibody product candidate strategies; risks related to the global impact of COVID-19; and other risks that are described in Sorrento's most recent periodic reports filed with the Securities and Exchange Commission, including Sorrento's Annual Report on Form 10-K for the year ended December 31, 2020, and subsequent Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission, including the risk factors set forth in those filings. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release and we undertake no obligation to update any forward-looking statement in this press release except as required by law.

Media and Investor Relations Contact Alexis Nahama, DVM (SVP Corporate Development) Email: mediarelations@sorrentotherapeutics.com

Sorrento and the Sorrento logo are registered trademarks of Sorrento Therapeutics, Inc.

G-MAB, DAR-T, SOFUSA, COVIGUARD, COVI-AMG, COVISHIELD, Gene-MAb, COVIDROPS, COVI-MSC, COVITRACK, COVITRACE and COVISTIX are trademarks of Sorrento Therapeutics, Inc.

SEMDEXA is a trademark of Semnur Pharmaceuticals, Inc.

ZTlido is a registered trademark owned by Scilex Pharmaceuticals Inc.

All other trademarks are the property of their respective owners.

2021 Sorrento Therapeutics, Inc. All Rights Reserved.

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Sorrento and Researchers at Karolinska Institutet Have Signed a Research Collaboration Agreement on iPSC-Derived Dimeric - GlobeNewswire

The regenerative medicine market size to grow at a CAGR of around 30% during the period – GlobeNewswire

New York, June 04, 2021 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Regenerative Medicine Market - Global Outlook and Forecast 2021-2026" - https://www.reportlinker.com/p06079941/?utm_source=GNW

Increased R&D investments by pharmaceutical companies will drive the demand for regenerative medicines. Europe plays a significant role in supporting the development and authorization of these products for several genetic and rare disorders. Increased funding via several venture capitalists and governments, and private institutions contribute significantly to the global regenerative medicine market growth. The increased prevalence of diseases such as cardiovascular diseases and diabetes can drive cell and gene therapy and tissue-engineered products. With the rise in thermal burns, occupational burn accidents, and chronic wounds, regenerative medicine products will experience steady growth. Novartis and Gilead Sciences are the key companies offering various therapies to treat cancer, genetic, and rare disorders.

The following factors are likely to contribute to the growth of the regenerative medicine market during the forecast period: Increase in the Patient Pool with Acute, Chronic, and Genetic Disorders Strong Pipeline Portfolio of Regenerative Medicine Companies Implementation of Advanced tissue-engineering Therapies Technology Faster Regulatory approvals

The report considers the present scenario of the regenerative medicine market and its market dynamics for 2019?2026. It covers a detailed overview of several market growth enablers, restraints, and trends. The study covers both the demand and supply sides of the market. It also profiles and analyzes leading companies and several other prominent companies operating in the market.

REGENERATIVE MEDICINE MARKET SEGMENTATION The regenerative medicine market research report includes a detailed segmentation by application, products, end-users, geography. Oncology constitutes the largest portion of the global regenerative medicine market share. The development of curative therapies by CAR-T and cell and gene therapies is widely popularized in the oncology therapeutic area. The increasing global prevalence rates and the increasing rates of different types of life-threatening cancers are the most important key factors that drive the oncology segment.

Consistent innovations in gene therapies due to the increased number of clinical trials and pipeline products are driving the growth prospects. Hence, the increased inflow of funding for the development of gene therapy is one of the driving factors for the sector growth Cell therapy is the major revenue contributor. The increasing prevalence of diabetes and foot ulcers is the primary factor contributing to the growth of tissue-engineered products. The tissue-engineered product segment to grow at a CAGR of 8% by 2026.

Hospitals are likely to remain a dominant revenue contributor to the global regenerative medicine market. Around 50% of therapeutic surgeries performed in the US annually, including cardiovascular and musculoskeletal, occur in hospitals. Cancer care centers are likely to witness an incremental growth of approx. USD 10 billion by 2026. As cancer is the second leading cause of death across the globe, which is responsible for approx. 10 million deaths annually, the scope of cancer centers is growing. Key vendors are focusing more on cancer care centers than hospitals to promote their products. As the cancer centers are being covered under reimbursement schemes, the growth of these facilities is likely to increase during the forecast period.

Segmentation by Application Oncology Genetic Disorders Dermatology Musculoskeletal Others

Segmentation by Product Gene Therapies Cell Therapies Tissue-Engineered Therapies

Segmentation by End-Users Hospitals Cancer Care Centers Wound Care Centers ASCs Others

INSIGHTS BY GEOGRAPHY In North America, the acceptance of regenerative medicine is relatively higher than in other developed countries. North America to accounts for the largest market share of the global regenerative medicine market. The growth can be primarily attributed to the increasing population with different types of cancers such as non-Hodgkin lymphoma, Hodgkin lymphoma, melanoma of the skin, and leukaemia in the North American region. Furthermore, North America consists of the highest number of regenerative medicine companies, which is adding to the market growth in the region. Europe has highly developed manufacturing facilities, which is driving the market growth in the European region. Most vendors in Europe depend on external sources for expansion and R&D activities.

Segmentation by Geography North America o US o Canada Europe o Germany o France o UK o Italy o Spain APAC o Japan o China o Australia o South Korea o India Latin America o Brazil o Mexico Middle East & Africa o Turkey o Saudi Arabia o South Africa o UAE

COMPETITIVE LANDSCAPE Amgen, Bristol Myers Squibb, Dendreon, F. Hoffmann-La Roche, Gilead Sciences, Novartis, Osiris, Organogenesis, and Vericel are the key vendors in the global regenerative medicine market. Global key players dominate the market shares due to wide distribution networks, innovative product launches, and broad product offerings. Companies are focusing on product innovations and strengthening their distribution channel to expand market presence globally. The market has developed innovative therapies in the field. For instance, Bristol Myers Squibb received approval from the US FDA for its product Lisocel - to treat relapsed/refractory diffuse large-B cell lymphoma (DLBCL) in February 2021. Small players are collaborating with prominent players to gain a competitive advantage in the market.

Key Vendors Novartis Gilead Sciences Amgen Organogenesis Bristol Myers Squibb Vericle Osiris Therapeutics

Other Prominent Vendors Anges Orchard Therapeutics Orthofix Integra Life Science MiMedx bluebird bio Mesoblast Avita Medical Takeda Pharmaceuticals Medipost TissueTech Misonix J-TEC Stempeutics CO.DON GC Pharma Orthocell Tego Science Nipro S-BIOMEDIC APAC Biotech Bio Solution Chiesi Farmaceutici Collplant Corestem Human Stem Cell Institute JCR Pharmaceuticals JW CreaGene Nuvasive Sibiono GeneTech Shanghai Sunway Biotech Terumo

KEY QUESTIONS ANSWERED: 1. How big is the regenerative medicine market? 2. What are the critical applications of regenerative medicine products? 3. Who are the key players in the regenerative medicine market? 4. Which segment accounted for the largest regenerative medicine market share? 5. Which region holds the largest share in the global regenerative medicine market? 6. How has the COVID-19 pandemic affected the regenerative medicine industry? Read the full report: https://www.reportlinker.com/p06079941/?utm_source=GNW

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Original post:
The regenerative medicine market size to grow at a CAGR of around 30% during the period - GlobeNewswire

Responses to Tafasitamab/Lenalidomide in DLBCL Sustained at Three Years – Cancer Network

Tafasitamab-cxix (Monjuvi) plus lenalidomide (Revlimid) for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) was capable of inducing sustained responses, according to 3-year follow-up data from the phase 2 L-MIND study (NCT02399085) presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.1

As of the data cutoff on October 30, 2020, the best objective response rate (ORR) was 57.5% (95% CI, 45.9-68.5) at a median follow-up of at least 35 months. Overall, 40% of patients experienced a complete response (CR) and 17.5% had a partial response (PR).

Median duration of response (DOR) was 43.9 months (95% CI, 26.1-NR).

The results of this long-term analysis of the L-MIND study demonstrate that tafasitamab plus lenalidomide followed by extended tafasitamab monotherapy provided durable responses in transplant-ineligible patients with relapsed or refractory DLBCL, coauthor Johannes Dll, MD, of Germanys University Hospital Wurzburg, said during a presentation of the data.

These data suggest that this chemotherapy-free combination treatment may have the potential to achieve prolonged remission and survival benefit in this patient population, especially at first relapse.

In the open-label, multinational, single-arm study, investigators assigned 81 patients with relapsed/refractory DLBCL to 12 mg/kg IV tafasitamab plus and 25 mg daily oral lenalidomide for up to 12 28-day cycles. Patients with stable disease or better then received the same dose of tafasitamab, an FC-modified humanized anti-CD19 monoclonal antibody, as monotherapy until disease progression.

Dll said that the best ORR was 67.5%, with a CR rate of 47.5% in patients who received 1 prior treatment. The ORR was 47.5% with a CR rate of 32.5% in patients who received 2 or more prior treatments.

The median progression-free survival (PFS) was 11.6 months and the overall survival (OS) of 33.5 months.

Dll noted that patients who had CR had better outcomes. The median DOR was not reached in this subgroup. Similarly, PFS (95% CI, 45.7-NR) and OS (95% CI, 45.7-NR) were not reached.

Concerning safety, long-term follow-up in the L-MIND study shows that tafasitamab plus lenalidomide was tolerated with no unexpected toxicities or new safety signals, Dll said. Similar to the primary analysis, the most common treatment-emergent adverse events of grade 3 or higher severity during the extended follow-up phase were neutropenia, thrombocytopenia, and febrile neutropenia.

Forty (49.4%) patients had grade 3 treatment-emergent neutropenia. Fourteen (17.3%) had grade 3 thrombocytopenia, while 10 (12.3%) had grade 3 febrile neutropenia.

The 3-year efficacy data, combined with the safety and tolerability profile of tafasitamab, further support a therapeutic option for patients with relapsed or refractory DLBCL who are ineligible for transplanta traditionally difficult-to-treat population, lead investigator Gilles Salles, MD, PhD, chief of the lymphoma service at Memorial Sloan Kettering Cancer Center, said in a news release.2

I am encouraged to see the confirmed favorable outcome of patients in the L-MIND study, which suggest that this combination treatment regimen could potentially offer a paradigm shift and long-term disease control, he added.

The FDA approved the tafasitamab/lenalidomide combination in July 2020 for the treatment of adult patients with relapsed/refractory DLBCL, including DLBCL arising from low-grade lymphoma, and who are not eligible for autologous stem cell transplant. The approval was based on previous data from L-MIND, which showed an ORR of 55%. The CR rate was 37% with a PR rate of 18%. The median DOR was 21.7 months.3

Findings from L-MIND later published in Lancet Oncology demonstrated even greater efficacy. At a median follow-up of 13.2 months, 60% (48/80; 95% CI, 48-71) of 80 patients who received the combination had an objective response with 34 (43%) CRs and 14 (18%) PRs.4

References

1. Dll J, Maddocks KJ, Gonzalez-Barca E, et al.Long-term analyses from L-MIND, a phase II study of tafasitamab (MOR208) combined with lenalidomide (LEN) in patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL). J Clin Oncol. 2021,39(suppl 15):7513. doi:10.1200/JCO.2021.39.15_suppl.7513

2. Incyte and MorphoSys announce 3-year results from phase 2 L-MIND study of tafasitamab in combination with lenalidomide for the treatment of relapsed or refractory DLBCL. News release. Incyte. June 4, 2021. Accessed June 5, 2021. https://bwnews.pr/3pnCVsi

3. FDA grants accelerated approval to tafasitamab-cxix for diffuse large B-cell lymphoma. FDA. Updated August 3, 2020. Accessed June 5, 2021. https://bit.ly/34Emq2z

4. Salles G, Duell J, Gonzlez Barca E, et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol. 2020 Jul;21(7):978-988. doi:10.1016/S1470-2045(20)30225-4

Read more:
Responses to Tafasitamab/Lenalidomide in DLBCL Sustained at Three Years - Cancer Network

‘Natural Killer Cells’ and Other Promising Cancer Treatments – Barron’s

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Last weekends online meeting of the American Association for Cancer Research gave a glimpse at the newest ideas for fighting cancer. Among the most exciting were treatments that engineer natural cells into cancer-targeting torpedoes.

Engineered-cell treatments from Affimed (ticker: AFMD), Fate Therapeutics (FATE), and Rubius Therapeutics (RUBY) drew attention from Wall Street analysts.

The German company Affimed reported exciting results in a four-patient test of its AFM13 antibodies in patients with the blood cancer lymphoma. When administered with a kind of immune cell known as a natural killer cell, Affimeds antibody binds the NK cells to a target found on many cancer cells.

Before treatment started at the end of last year, all four lymphoma patients had been very sick. One had even been consigned to hospice.

The cancer receded in all four patients after treatment, with complete responses in two of them. The patient who had been sent to hospice is now eligible for a bone-marrow transplant. Side effects werent a problem.

They had all failed multiple lines of treatmentup to 14 lines of therapy, said Katy Rezvani, a professor at the University of Texas MD Anderson Cancer Center who is leading the study, on a Thursday morning conference call. The fact that we are seeing responses as it is, I think, is just incredible.

Dose levels of the Affimed-primed killer cells were kept deliberately low in the first administrations of the treatment. Higher doses may show deeper response and greater persistence of the natural killer cells, notes BMO Capital Markets analyst Do Kim in a Thursday note. Affimed is testing other antibodies in Phase 1 studies that target solid tumors.

Excitement over the lymphoma study results lifted Affimed stock from about $7.70 to $10.70 since last week. In recent trading, the shares were down 9.3%, at $9.38, after the development-stage company reported a slightly higher-than-expected loss of 0.50 euros a share (about 60 cents) for the 2020 year. BMOs Kim rates Affimed at Outperform, with a $15 price target.

One promising feature of natural-killer-cell treatments is that the cells can be obtained from donors and stored on the shelf. Current treatments with other engineered immune cells must harvest a patients own cells, then modify and grow them for re-administration. Another pioneer in developing NK cell therapies is Fate Therapeutics, and the company provided several updates at the AACR meeting on its treatments.

Fates stock enjoyed a remarkable run in the past year, soaring from $19 to a January 2021 peak of $119, before settling back to a recent $84.87. That puts an $8 billion market cap on a company thats yet to report revenue. But Fate has 10 clinical trials in Phase 1 for its NK cell technology, which takes undifferentiated stem cells (stored on the shelf) and transforms them into NK cells targeting a variety of solid and blood tumors.

At AACR, Fate focused on its laboratory studies that show the flexibility of its NK cell technology. In planned meetings later this year, it will review its human trials against various cancers. The stocks gain has some analysts rating it Neutral. Among them is H.C. Wainwrights Robert Burns, who wrote in January about the excitement that followed Fates report that its treatment had reversed the cancer in a patient whose lymphoma had resisted seven other kinds of therapy.

Burns may have a Neutral rating on Fates stock, but he thinks it could rise to $108 as the company reports more clinical trial results this year. Thats a better than 25% upside.

One more engineered cell therapy discussed at AACR was the unusual approach of Rubius Therapeutics, which turns off-the-shelf red blood cells into therapies that stimulate an immune system attack on cancer. Researchers detailed results first reported in March, from a Phase 1 trial against several different cancers. The treatment reversed cancers in one patient with metastatic melanoma and another with metastatic anal cancer, while stabilizing the disease in six other patients.

Rubius will escalate doses in the Phase 1 study, while proceeding with other trials that target different kinds of cancer or combine its treatment with other cancer therapies. Guggenheims Michael Schmidt projects that Rubius could start to see revenue from its unique approach in 2024, and rates the stock a Buy. He argues that its stock, now trading at $23.86, is worth at least $30.

Write to Bill Alpert at william.alpert@barrons.com

Link:
'Natural Killer Cells' and Other Promising Cancer Treatments - Barron's

Capturing the Pandemic Experience in Haiku Poetry – Duke Today

The COVID-19 pandemic and the events since March 2020 left us with indelible experiences. From quirks of remote work to powerful emotions stemming from the way the pandemic intersects with our lives, poetry can be a healthy and fun way to process moments and feelings.

To celebrate International Haiku Poetry Day on April 17, Working@Duke asked staff and faculty to use the Japanese poetry form of haiku poems of three lines with five, seven and five syllables to share their unique expressions.

Enjoy the responses that were submitted by 5 p.m. on April 5:

Scrubs on, then scrubs off. Put others before ourselves. Eat, sleep, and repeat.

- Jamie Jill Maness, Clinical Nurse, DOCR

Were on the frontline. Were knocked down but we rise up. We are all Duke Strong.

- Jamie Eddy, LPN, Durham Pediatrics

Holds up the i-Pad. Family says goodbye from screen. Prayers. Last breaths taken.

- Ashley Acken, Senior Clinical Administrative Chaplain, Duke University Hospital

Mask over mouth, nose, Goggles fog with every breath. Protected, maybe?

- Katie Sanford, Physical Therapist, Duke Cardiopulmonary Rehabilitation

Masked heroes working. Saving lives every day. New day dawning soon.

- Dawn Jones Marshall, Medical Laboratory Scientist, Stem Cell Laboratory

Another long shift How do I avoid Covid? Scrubs in the washer

- Matt Mathias, Consulting Associate, Department of Family Medicine and Community Health

A novel virus, Invades our world quite quickly, Healthcare heroes win.

- Nathan Wise, Financial Analyst, Duke Raleigh Hospital

we fight the good fight over and over again all are heroes here

- Robin L. A. Clinedinst, Ophthalmic Technician, Duke Eye Center of South Durham

Death among many Heart break beyond repairing Good-by left unsaid

- Laurie Edgerton, Patient Service Associate, Duke Urgent Care South

As I close my eyes I am free no mask for me I know they'll miss me

- Odette Benschikovski, Clinical Nurse, Duke University Hospital

Bless the health workers Who put their own lives at risk So that all can live

- Megan Bell, Financial Services Specialist, Duke Credit Union

The pandemic world Little things have become big We need hugs again.

- Margaret (Peggy) Eren, Nurse Practitioner, Division of Cellular Therapy and Hematologic Malignancy

Get your vaccine To keep everyone healthy and protect the sick.

- Emily Escano, Administrative Assistant, Center for Advanced Practice

Cautionary tale. Science is manifested. The death toll rises.

- Robyn Miller, Departmental Director for Human Resources, School of Medicine, Orthopaedic Surgery

Masks on for safety. Let's get rid of this virus. Show our smiles again!

- Candace Martindale, Nursing Program Coordinator, Duke Home Care & Hospice

Swab in my nostril. Place the swab in the test tube. Safe campus for all.

- Elizabeth Cross, Surveillance Testing

Missing open arms Grandchildren question distance Love in both our eyes

- Valery Nelson, Laboratory Manager Bachelder Lab, School of Medicine

Ebb the tide today. Wash hands. Wear mask. Wait six feet. Protect those you love.

- Patricia H. Davis, Clinical Services Nurse, Adult Bone Marrow Transplant Clinic

My mask is on now But I can still enjoy life You are all precious

- Sally Hessnice, Clinical Nurse, Duke North OR

Daily fogged glasses Free stuff for healthcare workers Vaccinated, yay!

- Chelsea Walsh, Clinical Nurse, Duke Children's Health Center

Me, alone - Try to feel normal. Failing because it is not.

- Leah M. Kerr, Technical Services Processing Archivist, David M. Rubenstein Rare Book & Manuscript Library

A friend cuts my hair. Oops she says and starts to laugh. It will grow back soon.

- Blair Chesnut, Senior Analyst Programmer, Molecular Physiology

Diet and exercising... Why have thee forsaken me Cake, get in my mouth.

- Alpha Esser, Technical Trainer, Duke Clinical Research Institute

isolation under a cul-de-sac of stars

- Crystal Simone Smith, Humanities Unbounded Fellow, Duke University

Eyes convey all now With mask in place hiding lips Eyes above mask smile

- Melissa Reese, Lab Research Analyst, Stem Cell Laboratory

A new grandbaby Cannot meet; cannot hold yet Hopeful, so hopeful

- Lesley Stanford, Clinical Dietitian, Nutrition Services

My Heart has listened. To all the grief that is here. And transmutes to love.

- Sherry Short, Nurse Clinician, Center of Excellence

Last year is hindsight Feels like vision incomplete New year, please be clear!

- Danielle Wiggins, Assistant Director for PhD Programs, Nicholas School of the Environment

Glooming summertime A personal, small friend rolls Whilst watching COVID

- Adrianne N. Burton, Patient Service Associate, Duke Otolaryngology South Durham

Introverted me Now completely misses hugs And those who gave them

- Melissa Graham, Program Coordinator, Office of Curricular Affairs

A horrible dream. I wake up fearful at night. Believe and trust. Sleep.

- Valerie Riddick, Administrative Manager, Duke Health Development & Alumni Affairs

a knee on his neck okay til he cried mama now my mask is gone

- Alonzo Felder, IT Analyst, University Office of Information Technology

Big milestone events Lost in swirls of pandemic Not to be retrieved

- LeAnn Fulton, Clinical Research Associate, DCRI

You smile on the Zoom But I know you are weary Like the rest of us

- Marty Jarrell, Communications Director, Family Connects International

Zoom meetings the norm Duke has me working from home Love working at Duke

- Tara Parker, Staff Assistant, Duke Cancer Institute

Close my laptop lid... Get up from my office chair... Hi Honey, I'm home!"

- John H. Campbell, Information Security Analyst, Duke Health Technology Solutions

No commute today. I can read a book or sew. Makes me so happy.

- Lisa Powell, Financial Analyst II, Department of Ophthalmology

More time with my kid. Grateful for technology. The glass is half full.

- Allison Jardine, Administrative Assistant, DUHS Clinical Labs Human Resources

If I don't get out Of this work-from-home stupor I may scream real loud

- Kristin LoBiondo Pfeiffer, Communications Specialist, Student Affairs

Work with kids and zoom Can't wait for normal life to Resume very soon

- Saimia Baluch, Project Leader, DCRI

Grooming has gone bad But saving on lunch, gas, shirts Pandemic shut-in

- Karl Leif Bates, Director of Research Communications, Duke University

Reveling, home works Front porch, back porch, TV, books Pandemic be gone, Free me

- Valerie Fernandez, Manager, Coding Integrity Department

One dog in my lap. Another at my side, I like remote work best.

- Allison W. Spell, Senior Clinical Research Coordinator, Neurosurgery

COVID Communication Zoom safe space personal space When does it all in

- Pauline D. Stroud, Geriatric Resource Nurse, Duke Rehabilitation Institute

Kids are still at home. Driving me mad as a cow. Please help me. Bring wine.

- Cheryl Beth Munsell, Development Assistant, University Development

From my screen I watch A flower blooms, spring is here Four-thirty awaits

- Candice Sanford, DukeWELL Care Specialist, Duke Population Health Management Office

Zoom meetings aren't bad. Virtual backgrounds are fun... Wait... am I muted?

- Ryan Chung, IT Analyst, Enterprise and Devices Support

Day in and day out Together ALL of the time Cherish family

- Shellene Walker, Senior Project Manager, Office of Information Technology

Read more:
Capturing the Pandemic Experience in Haiku Poetry - Duke Today