Ten-Year Data from CheckMate -067 Trial Shows Long-Term Survival Benefits of Opdivo Plus Yervoy Combination in Advanced Melanoma

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Final efficacy and safety data from the Phase III CheckMate -067 trial (NCT01844505) demonstrated durable survival improvements over 10 years with the combination of first-line Opdivo (nivolumab) with Yervoy (ipilimumab) or Opdivo monotherapy compared with Yervoy monotherapy in patients with previously untreated advanced or metastatic melanoma.^1-3 The results, published by The New England Journal of Medicine,³ showed the longest reported median overall survival (OS) data for a Phase III advanced melanoma trial among patients administered the Opdivo plus Yervoy combination, according to the trial investigators.

“Just over a decade ago, an advanced melanoma diagnosis meant that you likely only had months to live. The dual immunotherapy combination of Opdivo plus Yervoy has radically changed this outlook for many of these patients,” Dana Walker, MD, MSCE, vice president, global program lead, melanoma and gastrointestinal and genitourinary cancers, Bristol Myers Squibb, in a press release. “Our goal was—and still is today—to redefine survival expectations for patients with melanoma; these data demonstrate our commitment to that objective and continue to provide hope.”¹

Opdivo is a monoclonal antibody that binds to the PD-1 receptor and inhibits tumor growth by improving T-cell function. 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.

Yervoy is a recombinant, human monoclonal antibody that attaches to the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), which is a negative T-cell activity regulator. By attaching to CTLA-4, Yervoy inhibits the interaction between CTLA-4 and its CD80/CD86 ligands. This action has been found to increase T-cell activation and proliferation, including tumor-infiltrating T-effector cells.

The double-blind, randomized CheckMate -067 trial compared the Opdivo plus Yervoy combination vs. Opdivo monotherapy or Yervoy monotherapy among 945 individuals who did not receive prior treatment for advanced melanoma. Patients randomly assigned to the Opdivo plus Yervoy cohort (n=314) were administered Opdivo 1 mg/kg plus Yervoy 3 mg/kg every three weeks (Q3W) for four doses followed by Opdivo 3 mg/kg every two weeks.

Patients randomly assigned to the Opdivo monotherapy cohort (n=316) were administered Opdivo 3 mg/kg Q2W plus placebo. Patients randomly assigned to the Yervoy monotherapy group (n=315) were administered Yervoy 3 mg/kg Q3W for four doses plus placebo. The trial’s primary endpoints were OS and progression-free survival, with secondary endpoints that include objective response rate (ORR), descriptive efficacy assessments, and safety.

At a minimum follow-up of 10 years, median OS was 71.9 months in the Opdivo plus Yervoy cohort compared with 36.9 months in the Opdivo monotherapy cohort and 19.9 months in the Yervoy monotherapy cohort. The hazard ratio for death was 0.53 (95% confidence interval [CI], 0.44 to 0.65) in the Opdivo plus Yervoy cohort compared to Yervoy monotherapy and 0.63 (95% CI, 0.52 to 0.76) in the Opdivo cohort compared to Yervoy monotherapy.³

Median melanoma-specific survival was more than 120 months in the Opdivo plus Yervoy cohort (not reached, 37% of patients alive at the end of the trial), compared to 49.4 months with Opdivo monotherapy and 21.9 months with Yervoy monotherapy.

Among those who were alive and progression-free at three years, 10-year melanoma-specific survival was 96% in the Opdivo plus Yervoy cohort compared to 97% with Opdivo monotherapy and 88% with Yervoy monotherapy.

“These data continue to demonstrate the impressive and durable clinical benefit of nivolumab in combination with ipilimumab with survival curves remaining stable for some years now,” James Larkin, PhD, FRCP, consultant medical oncologist, Department of Medical Oncology, The Royal Marsden, said in a press release. “Remarkably, 43% of patients treated with [Opdivo] and [Yervoy] are alive ten years later and many did not need subsequent therapy.”¹

Further, ORR after 10 years was 58.3% among those administered the combination of Opdivo plus Yervoy, 44.9% among those administered Opdivo monotherapy, and 9.0% among those administered Yervoy monotherapy.

In terms of safety, the profile of the Opdivo plus Yervoy combination was consistent with previous reports and no new safety signals were identified. Grade 3/4 treatment-related adverse events were reported by 62.6% of individuals in the Opdivo plus Yervoy cohort, 24.6% among patients in the Opdivo monotherapy cohort, and 29.6% among patients in the Yervoy cohort.

“As compared with ipilimumab monotherapy, nivolumab-containing therapies have continued to show a prolonged survival benefit in patients with advanced melanoma, with no new safety signals,” the study authors concluded. “These 10-year data underscore how immune checkpoint inhibitor therapy has helped to change the long-term prognosis for patients with advanced melanoma and highlight the potential for a cure in patients who have a response to this type of treatment.”³

References

1. Bristol Myers Squibb Presents Landmark 10-Year Follow-Up Data from CheckMate -067 Which Showed Continued Durable Long-Term Survival Benefit with Opdivo® plus Yervoy® in Advanced Melanoma. News release. Bristol Myers Squibb. September 15, 2024. Accessed September 16, 2024. https://news.bms.com/news/corporate-financial/2024/Bristol-Myers-Squibb-Presents-Landmark-10-Year-Follow-Up-Data-from-CheckMate--067-Which-Showed-Continued-Durable-Long-Term-Survival-Benefit-with-Opdivo-plus-Yervoy-in-Advanced-Melanoma/default.aspx

2. Phase 3 Study of Nivolumab or Nivolumab Plus Ipilimumab Versus Ipilimumab Alone in Previously Untreated Advanced Melanoma (CheckMate 067). ClinicalTrials.gov. July 7, 2024. Accessed September 16, 2024. https://clinicaltrials.gov/study/NCT01844505

3. Wolchok, J. et al. Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma. N Engl J Med . Published September 15, 2024. https://www.nejm.org/doi/full/10.1056/NEJMoa2407417?logout=true