Clinical Trial Data Presented at ASCO Show Efficacy of Opdivo-Based Combinations Treating Lung Cancer

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Results from a trio of clinical trials presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting demonstrated the efficacy of Opdivo (nivolumab) in the treatment of early stage and advanced non-small cell lung cancer (NSCLC).¹ Findings from the CheckMate -77T, CheckMate -816, and CheckMate -9LA trials show the potential of Opdivo to improve survival among patients with early and advanced stages of lung cancer, according to Bristol Myers Squibb.

“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,” Ian M. Waxman, MD, vice president, senior global program lead, late development, oncology, Bristol Myers Squibb, said in a press release. “At ASCO, 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.”¹

Opdivo is a monoclonal antibody that binds to the PD-1 receptor and inhibits tumor growth by improving T-cell function.^2,3 Opdivo has been approved across an array of indications, both as a single agent and in combination therapy, including for patients with unresectable or metastatic melanoma; metastatic NSCLC; advanced renal cell carcinoma; classical Hodgkin lymphoma; recurrent or metastatic squamous cell carcinoma of the head and neck; locally advanced or metastatic urothelial carcinoma; microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer; and hepatocellular carcinoma.²

The randomized, double-blind, placebo-controlled, multi-center Phase III CheckMate -77T trial analyzed a perioperative regimen of neoadjuvant Opdivo plus chemotherapy followed by surgery and adjuvant Opdivo in patients with stage III resectable NSCLC.

The results show that the combination improved median event-free survival (EFS), regardless of nodal status, including both 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) compared with neoadjuvant chemotherapy plus placebo followed by surgery and adjuvant placebo.

EFS rates at the one-year mark were higher among both subgroups in the perioperative Opdivo cohort (N2 70% vs. 45%, and non-N2 74% vs. 62%, respectively).

Following surgery, more patients administered Opdivo achieved a pathologic complete response vs. placebo in both the N2 (28.6% vs. 7.6%) and non-N2 (31.1% vs. 6.7%) subgroups. In terms of safety, among patients with N2 disease, grade 3–4 treatment-related adverse events (TRAEs) were reported in 34% of patients in the Opdivo cohort compared with 26% in the placebo cohort. Among patients with non-N2 disease, TRAEs were reported in 29% of patients in the Opdivo cohort and 21% of patients in the placebo cohort.

The randomized, open label, multi-center, Phase III CheckMate -816 trial analyzed Opdivo plus chemotherapy compared to chemotherapy alone in the neoadjuvant treatment of patients with resectable stage IB to IIIA NSCLC, regardless of PD-L1 expression.

At a median follow up of 57.6 months, neoadjuvant treatment with Opdivo plus chemotherapy showed a median EFS of 43.8 months compared with 18.4 months among patients in the chemotherapy alone cohort (HR, 0.66; 95% CI, 0.49 to 0.90).

Rates of four-year EFS were 49% in the neoadjuvant Opdivo plus chemotherapy cohort compared with 38% with chemotherapy alone. Overall survival (OS) did not achieve statistical significance; however, neoadjuvant treatment with Opdivo plus chemotherapy continued demonstrating a clinically important OS improvement trend compared with chemotherapy alone (HR, 0.71; 98.36% CI, 0.47 to 1.07), according to the investigators.

The results show that 71% of patients administered neoadjuvant Opdivo plus chemotherapy were alive at the four-year mark compared with 58% of patients administered chemotherapy alone. There were no new safety signals reported among patients administered neoadjuvant Opdivo plus chemotherapy at the extended follow-up.

The open-label, global, multi-center, randomized, Phase III CheckMate -9LA trial compared Opdivo plus Yervoy (ipilimumab) combined with two cycles of chemotherapy vs. chemotherapy alone in the first-line treatment of patients with metastatic NSCLC regardless of PD-L1 expression and histology.

Five-year follow-up data demonstrated a durable, long-term survival benefit among patients administered Opdivo plus Yervoy combined with two cycles of chemotherapy vs. chemotherapy alone.

At a minimum follow-up of 57.3 months, 18% of patients in the Opdivo plus Yervoy cohort were alive at five years compared to 11% of patients in the chemotherapy alone cohort (HR, 0.73, 95% CI, 0.62 to 0.85). The five-year survival rate among patients with tumor PD-L1 <1% administered the Opdivo plus Yervoy combination was 22% compared to 8% among patients administered chemotherapy alone (HR, 0.63; 95% CI, 0.49 to 0.83). There were no new safety signals reported with the Opdivo plus Yervoy combination in the extended follow-up.

References

1. Bristol Myers Squibb Presents Multiple New Analyses at 2024 ASCO® Annual Meeting Highlighting Opdivo and Opdivo-based Combinations in Early and Advanced Stages of Non-Small Cell Lung Cancer. News release. Bristol Myers Squibb. June 3, 2024. Accessed June 3, 2024. https://news.bms.com/news/corporate-financial/2024/Bristol-Myers-Squibb-Presents-Multiple-New-Analyses-at-2024-ASCO-Annual-Meeting-Highlighting-Opdivo-and-Opdivo-based-Combinations-in-Early-and-Advanced-Stages-of-Non-Small-Cell-Lung-Cancer/default.aspx

2. Opdivo. Prescribing information. Bristol Myers Squibb; 2021. Accessed June 3, 2024. https://packageinserts.bms.com/pi/pi_opdivo.pdf

3. FDA approves first immunotherapy for initial treatment of gastric cancer. News release. FDA. April 16, 2021. Accessed June 3, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-immunotherapy-initial-treatment-gastric-cancer.