The European Commission (EC) has approved the combination of Opdivo (nivolumab) and Yervoy (ipilimumab) in the treatment of patients diagnosed with BRAF V600 wild-type unresectable or metastatic melanoma. This is the first and only combination treatment of two immuno-oncology agents approved in the European Union (EU).
On the basis of the approval were the results of CheckMate-067, a Phase 3, double-blind, randomized clinical trial evaluating Opdivo and Yervoy as a combination therapy — versus either drug as a monotherapy — in 945 patients with previously untreated advanced melanoma. Its primary endpoints are objective response rate (ORR) and progression-free survival (PFS).
Results revealed the regimen’s positive results in previously untreated patients, as measured by improvements in confirmed ORR and PFS. Those treated with the combined regimen exhibited superior improvements compared to those who received monotherapy with either one of the two immuno-oncology agents.
Dr. James Larkin, from The Royal Marsden and lead author on CheckMate – 067, the trial that led to this approval, commented in a press release, “Historically, advanced melanoma has been a very difficult-to-treat disease. Now, with this approval, patients in Europe will have a treatment option combining two Immuno-Oncology therapies, Opdivo and Yervoy, which in a Phase 3 randomized trial has shown its ability to deliver superior efficacy versus Yervoy monotherapy in progression-free survival and response. This is truly good news for healthcare providers and the patients they treat, as it represents an important new treatment option with the potential for improved outcomes.”
Results from the CheckMate-067 trial showed that the combined regimen resulted in a 58% reduction in the risk of disease progression compared to Yervoy single-agent while Opdivo single-agent showed a 45% risk reduction versus Yervoy single-agent.
At a minimum follow-up of 18 months, the median PFS for the combined regimen was 11.5 months and 6.9 months for Opdivo single-agent versus 2.89 months for Yervoy single-agent.
Based on the CheckMate -067 trial data, the EC adopted the Committee for Medicinal Products for Human Use (CHMP) recommendation to include a report to the broad indication that relative to Opdivo monotherapy, an increase in PFS for the combination of Opdivo with Yervoy is established only in patients with low tumor PD-L1 expression.
In the trial, ORR was superior for the combination regimen in comparison with Opdivo single-agent across tumor PD-L1 expression levels.
The EC approval was also based on data from CheckMate 069 a Phase 2, double-blind, randomized trial evaluating Opdivo + Yervoy combined regimen versus Yervoy single-agent in 142 patients with previously untreated unresectable or metastatic melanoma, including patients with BRAF V600 mutation positive and BRAF wild-type advanced melanoma.
The results showed that the combined regimen showed an ORR of 61% in patients with BRAF wild-type advanced melanoma, versus an ORR of 11% in patients treated with the Yervoy single-agent.
The 12- and 18-month estimated OS rated were 79% and 73%, respectively, for the combined regimen, and 62% and 56% for Yervoy single-agent.
Emmanuel Blin, senior vice president, Head of Commercialization, Policy and Operations, Bristol-Myers Squibb, commented, “Today’s approval of the Opdivo + Yervoy Regimen for advanced melanoma patients supports our goal of developing innovative treatment approaches that have the potential to improve patient outcomes. The Opdivo + Yervoy Regimen is the first and only approved Immuno-Oncology combination, and only Regimen to deliver superior efficacy compared to Yervoy, and we are thrilled to make this novel combination treatment available to patients with advanced melanoma in Europe.”