On June 3, 2024 Bristol Myers Squibb (NYSE: BMY) reported results from three updated analyses from the CheckMate -77T, CheckMate -816, and CheckMate -9LA studies supporting Opdivo (nivolumab) and Opdivo-based combinations in early stage and advanced non-small cell lung cancer (NSCLC) (Press release, Bristol-Myers Squibb, JUN 3, 2024, View Source [SID1234643998]). Data are being presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting from May 31 to June 4, 2024, in Chicago, IL.

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"Our research and development efforts in NSCLC are marked both by our continuing strength in immunotherapy and by targeted approaches that offer new options for patients with challenging mutations," said Ian M. Waxman, M.D., vice president, senior global program lead, late development, oncology, Bristol Myers Squibb. "At ASCO (Free ASCO Whitepaper), we are presenting studies that demonstrate the impact of immunotherapy earlier in the course of disease, including for those whose tumors may be removed by surgery, to help prevent recurrence. These studies, in addition to updates for patients with advanced disease, are reinforcing the growing body of evidence around our thoracic portfolio and our progress toward delivering options that improve the hope of survival."

The immunotherapy analyses were presented as part of a larger collection of studies across the company’s lung cancer portfolio. Other presentations include an updated analysis of the Phase 1/2 TRIDENT-1 study which shows Augtyro (repotrectinib) continued to demonstrate durable responses in ROS1-positive TKI-naive NSCLC patients at a follow-up of approximately three years. Additionally, data from the Phase 3 KRYSTAL-12 study of KRAZATI (adagrasib) showed a statistically significant improvement in progression-free survival (PFS) compared to docetaxel in patients with previously treated KRASG12C-mutated NSCLC.

CheckMate -77T Results

A late-breaking exploratory analysis from the Phase 3 CheckMate -77T study evaluating the perioperative regimen of neoadjuvant Opdivo with chemotherapy followed by surgery and adjuvant Opdivo in patients with stage III resectable NSCLC was presented today in an oral presentation (Abstract #LBA8007). In the analysis, the perioperative Opdivo regimen improved median event-free survival (EFS) regardless of nodal status, including in the N2 subgroup (30.2 vs. 10.0 months; HR, 0.46; 95% CI, 0.30–0.70) and non-N2 subgroup (NR vs. 17.0 months; HR, 0.60; 95% CI, 0.33-1.08) versus neoadjuvant chemotherapy and placebo followed by surgery and adjuvant placebo. One-year EFS rates were higher in both subgroups with the perioperative Opdivo regimen (N2 70% vs. 45%, and non-N2 74% vs. 62%, respectively). Surgical feasibility was similar between patients with N2 and non-N2 disease and was also similar between the Opdivo and placebo arms (77% vs. 73% among patients with N2 status; 82% vs. 79% among patients with non-N2). After surgery, a higher proportion of patients in the Opdivo arm had a pathologic complete response compared with placebo in both N2 (28.6% vs. 7.6%) and non-N2 (31.1% vs. 6.7%) subgroups. Grade 3–4 treatment-related adverse events (TRAEs) occurred in 34% and 26% in patients with N2 disease and 29% and 21% of patients with non-N2 disease with the perioperative Opdivo regimen and placebo regimen, respectively. These data represent a comprehensive analysis by nodal status among patients with stage III resectable NSCLC from a global Phase 3 study of perioperative immunotherapy.

CheckMate -77T is the company’s second positive randomized Phase 3 trial with an immunotherapy-based combination for the treatment of resectable non-metastatic NSCLC. Data from CheckMate –77T’s primary analysis supported the regulatory filing acceptances for the perioperative Opdivo-based regimen by the U.S. Food and Drug Administration and European Medicines Agency in February 2024.

CheckMate -816 Results

Four-year survival data from the Phase 3 CheckMate -816 study, representing the longest follow-up among all global Phase 3 studies evaluating neoadjuvant or perioperative immunotherapy-based treatments for stage IB-IIIA resectable NSCLC, were also presented in a rapid oral session on June 2 (Abstract #LBA8010). With a median follow up of 57.6 months, neoadjuvant Opdivo with chemotherapy continued to improve EFS versus chemotherapy alone (median: 43.8 months vs. 18.4 months; HR, 0.66; 95% CI, 0.49 to 0.90). Four-year EFS rates were higher in the neoadjuvant Opdivo with chemotherapy arm (49% vs. 38%). While overall survival (OS) did not meet statistical significance at this analysis, neoadjuvant Opdivo with chemotherapy continued to show a clinically important OS improvement trend over chemotherapy alone (HR, 0.71; 98.36% CI, 0.47 to 1.07). At four years, 71% of patients treated with neoadjuvant Opdivo and chemotherapy were alive, compared to 58% with chemotherapy alone. OS will continue to be followed. An exploratory analysis of lung cancer-specific survival in this study also showed a consistent trend with OS, favoring neoadjuvant Opdivo with chemotherapy (HR, 0.62; 95% CI, 0.41-0.93). No new safety signals were observed with neoadjuvant Opdivo with chemotherapy at the extended follow-up.

CheckMate -9LA Results

Finally, five-year follow-up results from the Phase 3 CheckMate -9LA study, showing durable, long-term survival benefits with Opdivo plus Yervoy (ipilimumab) combined with two cycles of chemotherapy compared to chemotherapy alone as a first-line treatment in patients with metastatic NSCLC were presented. With a minimum follow-up of 57.3 months, the dual immunotherapy-based combination continued to improve OS, with 18% of patients treated with Opdivo plus Yervoy with two cycles of chemotherapy alive at five years compared to 11% of patients treated with chemotherapy alone (HR, 0.73, 95% CI, 0.62 to 0.85). The five-year survival rate for patients with tumor PD-L1 <1% (a patient population with high unmet need) who were treated with Opdivo plus Yervoy with two cycles of chemotherapy was more pronounced at 22% compared to 8% for patients treated with chemotherapy alone (HR, 0.63; 95% CI, 0.49 to 0.83).

At the 5-year landmark analysis, responses were more durable in the Opdivo plus Yervoy plus chemotherapy arm with 19% of patients still in response compared to 8% for chemotherapy alone. The benefit of Opdivo plus Yervoy with two cycles of chemotherapy was maintained across all secondary endpoints and subgroups of interest.

No new safety signals were observed with Opdivo plus Yervoy with two cycles of chemotherapy with this extended follow-up.

Opdivo and Opdivo-based combinations are approved in four indications in NSCLC, including in neoadjuvant and metastatic treatment settings.

Bristol Myers Squibb thanks the patients and investigators participating in the CheckMate -816, CheckMate -77T and CheckMate -9LA clinical trials.

About CheckMate -77T

CheckMate -77T is a Phase 3 randomized, double-blind, placebo-controlled, multi-center trial evaluating neoadjuvant Opdivo with chemotherapy followed by surgery and adjuvant Opdivo versus neoadjuvant placebo plus chemotherapy followed by surgery and adjuvant placebo in 461 patients with resectable stage IIA to IIIB NSCLC. The primary endpoint of the trial is EFS. Secondary endpoints include OS, pathologic complete response and major pathologic response.

About CheckMate -816

CheckMate -816 is a Phase 3 randomized, open label, multi-center trial evaluating Opdivo with chemotherapy compared to chemotherapy alone as neoadjuvant treatment in patients with resectable stage IB to IIIA NSCLC (per the 7th edition American Joint Committee on Cancer/Union for International Cancer Control staging criteria), regardless of PD-L1 expression. For the primary analysis, 358 patients were randomized to receive either Opdivo 360 mg plus histology-based platinum doublet chemotherapy every three weeks for three cycles, or platinum doublet chemotherapy every three weeks for three cycles, followed by surgery. The primary endpoints of the trial are EFS and pathologic complete response. Secondary endpoints include OS, major pathologic response, and time to death or distant metastases.

About CheckMate -9LA

CheckMate -9LA is an open-label, global, multi-center, randomized Phase 3 trial evaluating Opdivo (360 mg Q3W) plus Yervoy (1 mg/kg Q6W) combined with chemotherapy (two cycles) compared to chemotherapy alone (up to four cycles followed by optional pemetrexed maintenance therapy if eligible) as a first-line treatment in patients with metastatic NSCLC regardless of PD-L1 expression and histology. Patients in the experimental arm (n=361) were treated with immunotherapy for up to two years or until disease progression or unacceptable toxicity. Patients in the control arm (n=358) were treated with up to four cycles of chemotherapy and optional pemetrexed maintenance (if eligible) until disease progression or unacceptable toxicity. The primary endpoint of the trial was OS in the intent-to-treat population. Secondary hierarchical endpoints included PFS and overall response rate, and the study also evaluated efficacy measures according to biomarkers.

About Lung Cancer

Lung cancer is the leading cause of cancer deaths globally. Non-small cell lung cancer (NSCLC) is one of the most common types of lung cancer, representing up to 84% of diagnoses. Non-metastatic cases account for the majority of NSCLC diagnoses (approximately 60%, with up to half of these being resectable), and the proportion is expected to grow over time with enhanced screening programs. While many non-metastatic NSCLC patients are cured by surgery, 30% to 55% develop recurrence and die of their disease despite resection, contributing to a need for treatment options administered before surgery (neoadjuvant) and/or after surgery (adjuvant) to improve long-term outcomes.