Details Category: Antibodies Published on Tuesday, 22 September 2020 10:41 Hits: 601

Adjuvant Opdivo doubled disease-free survival; is the first therapeutic option to show statistically significant and clinically meaningful disease-free survival benefit in these patients, regardless of tumor histology, following chemoradiation therapy and resection

Results from Phase 3 CheckMate -577 trial selected for presentation during a Presidential Symposium at the European Society for Medical Oncology Virtual Congress 2020

PRINCETON, NJ, USA I September 21, 2020 I Bristol Myers Squibb (NYSE: BMY) today announced first results from the Phase 3 CheckMate -577 trial in which adjuvant treatment with Opdivo (nivolumab) showed a statistically significant and clinically meaningful improvement in disease-free survival (DFS), the trials primary endpoint, compared to placebo in patients with esophageal or gastroesophageal junction (GEJ) cancer following neoadjuvant chemoradiation therapy (CRT) and tumor resection. The current standard of care for patients with esophageal or GEJ cancer following neoadjuvant CRT and tumor resection is surveillance. These results signify the first time an adjuvant therapeutic option has significantly prolonged DFS for patients in this setting.

Median DFS was doubled in patients receiving Opdivo [22.4 months; (95% Confidence Interval [CI]: 16.6 to 34.0)] compared to those receiving placebo after surgery [11.0 months; (95% CI: 8.3 to 14.3)] (Hazard Ratio [HR] 0.69; 96.4% CI: 0.56 to 0.86; p=0.0003). The median duration of treatment for patients in the Opdivo arm was just over 10 months [10.1 months (<0.1 to 14.2)] versus nine months for patients in the placebo arm [9.0 months (<0.1 to 15)]. The safety profile of Opdivo in CheckMate -577 was consistent with previously reported studies of Opdivo monotherapy.

While about 25% to 30% of patients with esophageal or gastroesophageal junction cancer achieve a complete response following chemoradiation therapy and surgery, the remaining 70% to 75% do not, and there is currently no adjuvant treatment option available for these patients with the potential to improve their outcomes, said Ronan J. Kelly M.D., MBA, Director, Charles A. Sammons Cancer Center at Baylor University Medical Center. Adjuvant treatment with nivolumab in the CheckMate -577 trial doubled patients time without disease recurrence, representing the first adjuvant treatment advancement for these patients with esophageal or gastroesophageal junction cancer.

Opdivo was well tolerated with an acceptable safety profile relative to placebo. The majority of patients in the Opdivo arm (89%) were able to receive a relative dose intensity of 90%. The incidence of any treatment-related adverse events (TRAEs), including any grade and Grade 3-4, was 71% and 13% among patients treated with Opdivo compared to 46% and 6% among patients receiving placebo. Serious TRAEs of any grade and Grade 3-4 occurred in less than 10% of patients treated with Opdivo (any grade in 8%, Grade 3-4 in 5%) compared to 3% and 1% of patients receiving placebo, with a low rate of any grade treatment-related discontinuations in both arms (9% for Opdivo vs. 3% in placebo).

These results make esophageal and gastroesophageal junction cancer the second cancer type following melanoma where Opdivo has demonstrated a benefit in the adjuvant setting, indicating the potential for Opdivo to become a new standard of care for these patients, said Ian M. Waxman, M.D., development lead, Gastrointestinal Cancers, Bristol Myers Squibb. This advancement showcases our commitment to evaluating our therapies in earlier stages of disease where we may be able to have a greater impact on preventing disease recurrence and improving patient outcomes. We look forward to discussing these encouraging results from CheckMate -577 with global health authorities in the coming months.

These data (Presentation #LBA9) will be featured in a Presidential Symposium at the European Society for Medical Oncology (ESMO) Virtual Congress 2020 on September 21 from 19:31-19:43 CEST.

About CheckMate -577

CheckMate -577 is a Phase 3 randomized, multi-center, double-blind study evaluating Opdivo as an adjuvant therapy in patients with resected esophageal or GEJ cancer who have received neoadjuvant CRT therapy and have not achieved a pathological complete response. The primary endpoint of the trial is DFS and the secondary endpoint is overall survival (OS). Following neoadjuvant CRT therapy and complete tumor surgical resection (also known as trimodality therapy), a total of 794 patients were randomized to receive placebo (n=262) or Opdivo (n=532) 240 mg by intravenous infusion every two weeks for 16 weeks followed by Opdivo 480 mg every four weeks until disease recurrence, unacceptable toxicity or withdrawal of consent, with a maximum of one year total treatment duration.

About Esophageal Cancer

Esophageal cancer is the seventh most common cancer and the sixth leading cause of death from cancer worldwide, with approximately 572,000 new cases and over 508,000 deaths in 2018. The two most common types of esophageal cancer are squamous cell carcinoma and adenocarcinoma, which account for approximately 85% and 15% of all esophageal cancers, respectively, though esophageal tumor histology can vary by region with the highest rate of esophageal adenocarcinoma occurring in North America (65%). The majority of cases are diagnosed in the advanced setting and impact a patients daily life, including their ability to eat and drink.

About Gastric Cancer

Gastric cancer, also known as stomach cancer, is the fifth most common cancer and the third leading cause of cancer death worldwide, with over 1,000,000 new cases and approximately 783,000 deaths in 2018. There are several cancers that can be classified as gastric cancer, including certain types of cancers that form in the GEJ, the area of the digestive tract where the esophagus and stomach connect. While GEJ cancer has a lower prevalence than gastric cancer, it continues to rise.

Bristol Myers Squibb: Advancing Cancer Research

At Bristol Myers Squibb, patients are at the center of everything we do. The goal of our cancer research is to increase patients quality of life, long-term survival and make cure a possibility. We harness our deep scientific experience, cutting-edge technologies and discovery platforms to discover, develop and deliver novel treatments for patients.

Building upon our transformative work and legacy in hematology and Immuno-Oncology that has changed survival expectations for many cancers, our researchers are advancing a deep and diverse pipeline across multiple modalities. In the field of immune cell therapy, this includes registrational CAR T cell agents for numerous diseases, and a growing early-stage pipeline that expands cell and gene therapy targets, and technologies. We are developing cancer treatments directed at key biological pathways using our protein homeostasis platform, a research capability that has been the basis of our approved therapies for multiple myeloma and several promising compounds in early- to mid-stage development. Our scientists are targeting different immune system pathways to address interactions between tumors, the microenvironment and the immune system to further expand upon the progress we have made and help more patients respond to treatment. Combining these approaches is key to delivering potential new options for the treatment of cancer and addressing the growing issue of resistance to immunotherapy. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines a reality for patients.

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the bodys own immune system to help restore anti-tumor immune response. By harnessing the bodys own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivos leading global development program is based on Bristol Myers Squibbs scientific expertise in the field of Immuno-Oncology, and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Companys Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

INDICATIONS

OPDIVO (nivolumab), as a single agent, is indicated for the treatment of patients with unresectable or metastatic melanoma.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

OPDIVO (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.

OPDIVO (nivolumab) is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with progression after platinum-based chemotherapy and at least one other line of therapy. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of patients with intermediate or poor risk, previously untreated advanced renal cell carcinoma (RCC).

OPDIVO (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.

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

OPDIVO (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab) 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 overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), 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 overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO (nivolumab) is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.

OPDIVO (nivolumab) is indicated for the treatment of patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.

CheckMate Trials and Patient Populations

Checkmate 037previously treated metastatic melanoma; Checkmate 066previously untreated metastatic melanoma; Checkmate 067previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 227previously untreated metastatic non-small cell lung cancer, in combination with YERVOY; Checkmate 9LApreviously untreated recurrent or metastatic non-small cell lung cancer in combination with YERVOY and 2 cycles of platinum-doublet chemotherapy by histology; Checkmate 017second-line treatment of metastatic squamous non-small cell lung cancer; Checkmate 057second-line treatment of metastatic non-squamous non-small cell lung cancer; Checkmate 032small cell lung cancer; Checkmate 025previously treated renal cell carcinoma; Checkmate 214previously untreated renal cell carcinoma, in combination with YERVOY; Checkmate 205/039classical Hodgkin lymphoma; Checkmate 141recurrent or metastatic squamous cell carcinoma of the head and neck; Checkmate 275urothelial carcinoma; Checkmate 142MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Checkmate 040hepatocellular carcinoma, as a single agent or in combination with YERVOY; Checkmate 238adjuvant treatment of melanoma; Attraction-3esophageal squamous cell carcinoma

About the Bristol Myers Squibb and Ono Pharmaceutical Collaboration

In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies as single agents and combination regimens for patients with cancer in Japan, South Korea and Taiwan.

About Bristol Myers Squibb

Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.

Celgene and Juno Therapeutics are wholly owned subsidiaries of Bristol-Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol Myers Squibb company and Juno Therapeutics, a Bristol Myers Squibb company.

SOURCE: Bristol-Myers Squibb

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Opdivo (nivolumab) Demonstrated Superior Disease-Free Survival in Patients with Resected Esophageal or Gastroesophageal Junction Cancer Compared to...