Bristol Myers Squibb Updates on Phase 3 CheckMate -73L Trial

Bristol Myers Squibb (NYSE: BMY) has announced that its Phase 3 CheckMate -73L trial did not achieve its primary endpoint of progression-free survival (PFS) in patients with unresectable, locally advanced stage III non-small cell lung cancer (NSCLC). The CheckMate -73L trial compared the efficacy of Opdivo® (nivolumab) in conjunction with concurrent chemoradiotherapy (CCRT) followed by Opdivo plus Yervoy® (ipilimumab) against CCRT followed by durvalumab.

The adverse events observed with the combination of Opdivo and CCRT followed by Opdivo plus Yervoy were largely consistent with known profiles of the individual components used in the treatment. According to Joseph Fiore, Vice President and Global Program Lead for Thoracic Cancers at Bristol Myers Squibb, the addition of immunotherapy to definitive chemoradiation did not yield better PFS outcomes in this context. Nevertheless, Fiore emphasized the ongoing need to enhance long-term outcomes for these patients and noted that the trial's results will inform future drug development efforts.

Bristol Myers Squibb has pledged to perform a comprehensive analysis of the data and collaborate with investigators to disseminate the findings to the scientific community. Despite the setback with CheckMate -73L, Opdivo and its combinations have demonstrated positive outcomes and are recognized as approved treatment options for patients with resectable or metastatic NSCLC.

The CheckMate -73L trial was a Phase 3, randomized, open-label study that enrolled 925 patients with previously untreated, locally advanced stage III NSCLC who were not suitable candidates for curative surgery. Participants were randomized into three arms: Arm A received Opdivo combined with CCRT followed by Opdivo plus Yervoy; Arm B received Opdivo combined with CCRT followed by Opdivo monotherapy; and Arm C received CCRT followed by durvalumab. The trial's primary endpoint was PFS as determined by RECIST 1.1 per blinded independent central review (BICR) for Arm A compared to Arm C. Secondary endpoints included overall survival (OS) across all study arms, PFS by RECIST 1.1 per BICR across the study arms, objective response rate (ORR), time to response (TTR), and duration of response (DOR) per RECIST 1.1 per BICR, along with additional safety and efficacy endpoints.

Lung cancer remains the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for up to 84% of lung cancer diagnoses. Non-metastatic NSCLC represents about 60% of the cases, with a significant fraction being resectable. Despite many non-metastatic NSCLC patients undergoing curative surgery, 30% to 55% experience recurrence and succumb to the disease. This highlights the necessity for effective treatment options both before (neoadjuvant) and after surgery (adjuvant) to improve long-term survival.

Bristol Myers Squibb has a clear mission: to transform patients' lives through scientific advancements. Their objective in cancer research is to develop medicines that offer improved, healthier lives for each patient and to make a cure a viable possibility. With a history of altering survival expectations across various cancers, the company’s researchers are pushing the boundaries in personalized medicine and leveraging innovative digital platforms to gain insights from data, thereby refining their focus.

Opdivo, a programmed death-1 (PD-1) immune checkpoint inhibitor, is designed to utilize the body’s immune system to restore anti-tumor responses. As a crucial treatment option for multiple cancers, Opdivo's global development program is extensive, involving numerous clinical trials across different phases and tumor types. Since its first regulatory approval in July 2014, Opdivo has treated over 35,000 patients and is approved in more than 65 countries. The combination of Opdivo and Yervoy was the first Immuno-Oncology regimen approved for metastatic melanoma treatment in October 2015 and is now approved in over 50 countries.

Yervoy is a recombinant, human monoclonal antibody that targets the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), enhancing T-cell activity. Initially approved by the U.S. FDA in 2011 for metastatic melanoma, Yervoy is part of an ongoing development program spanning multiple tumor types.