EC approves Opdivo + Yervoy regimen for advanced melanoma

The European Commission (EC) has approved Bristol-Myers Squibb’s Opdivo in combination with Yervoy for the treatment of advanced (unresectable or metastatic) melanoma in adults.

This represents the first and only approved combination of two Immuno-Oncology agents in the European Union (EU). This approval allows for the marketing of the Opdivo + Yervoy Regimen in all 28 Member States of the EU. Approval was based on CheckMate -067, the first Phase III, double-blind, randomised study, in which the Opdivo + Yervoy Regimen and Opdivo monotherapy demonstrated superior progression-free survival (PFS) and objective response rates (ORR) in patients with advanced melanoma, regardless of BRAF mutational status, versus Yervoy alone. The safety profile was consistent with previously reported studies evaluating the Opdivo +Yervoy Regimen, and most treatment-related adverse events were managed using established algorithms.

Dr James Larkin, from The Royal Marsden and lead author on CheckMate – 067, commented, “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 III randomised trial has shown its ability to deliver superior efficacy versusYervoy 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.”

Opdivo + Yervoy Regimen demonstrated a 58% reduction in the risk of disease progression

In study CheckMate -067, the Opdivo + Yervoy Regimen demonstrated a 58% reduction in the risk of disease progression versus Yervoy monotherapy in previously untreated patients with advanced melanoma, while Opdivo monotherapy demonstrated a 45% risk reduction versus Yervoy monotherapy. The median PFS for the Opdivo + YervoyRegimen was 11.5 months and 6.9 months for Opdivo monotherapy versus 2.89 months for Yervoy monotherapy, at a minimum follow-up of 18 months. The Opdivo + Yervoy Regimen and Opdivo monotherapy also demonstrated a higher ORR (ORR: 58% and 44%, respectively) versus Yervoy monotherapy (19%). Median duration of response was not reached for the Opdivo + Yervoy Regimen and was 22.3 months for Opdivo monotherapy, versus 14.4 months for Yervoy alone.

Based on a pre-planned, descriptive analysis of data from CheckMate -067, the EC adopted the Committee for Medicinal Products for Human Use (CHMP) recommendation to add an informative statement 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 tumour PD-L1 expression. In the study, overall response rates were higher for the combination of Opdivo and Yervoy relative to Opdivomonotherapy across tumour PD-L1 expression levels.

The approval was also based on supportive data from the Phase II study, CheckMate -069, in which the Opdivo + Yervoy Regimen demonstrated an ORR, the primary endpoint, of 61% in patients with BRAF wild-type advanced melanoma, versus 11% ORR in the Yervoy monotherapy arm, with a minimum follow-up of 11 months.

Emmanuel Blin, senior vice president, Head of Commercialization, Policy and Operations, Bristol-Myers Squibb, commented, “The Opdivo + YervoyRegimen 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.”