Bristol Myers Squibb Receives EC Approval for Opdivo plus Yervoy with Limited Chemotherapy as First-Line Treatment for Metastatic NSCLC

Compiled by Hemingway

On November 6, Bristol-Myers Squibb (BMS) announced that the European Commission (EC) has approved the dual immunotherapy regimen of nivolumab (Opdivo) and ipilimumab (Yervoy) (“O+Y”) as a first-line treatment for adult patients with metastatic non-small cell lung cancer (NSCLC) who have received two cycles of platinum-based chemotherapy.

This regimen is the first dual immunotherapy approved by the European Commission for the treatment of non-small cell lung cancer (NSCLC), and it also represents the third indication approved in the European Union for the “O+Y”-based regimen, following metastatic melanoma and advanced renal cell carcinoma.

In addition to the European Union, the combination of “O+Y” with two cycles of chemotherapy has been approved for first-line treatment of patients with metastatic NSCLC in 11 countries/regions, including the United States.

This approval was based on the results of the Phase III CheckMate -9LA clinical trial. In patients with metastatic non-small cell lung cancer (NSCLC) without EGFR or ALK positive mutations, regardless of PD-L1 expression levels, patients achieved clinically meaningful overall survival benefits after receiving two cycles of concurrent "O+Y" dual immunotherapy.

CheckMate -9LA is an open-label, multicenter, randomized Phase III clinical trial evaluating the feasibility and safety of Opdivo (360 mg Q3W) plus Yervoy (1 mg/kg Q6W) in combination with chemotherapy (two cycles) versus chemotherapy alone (with optional pemetrexed maintenance therapy for up to four cycles, if eligible) as a first-line treatment regimen for patients with metastatic NSCLC, regardless of PD-L1 expression levels and histological subtypes.

Experimental group (n = 361): Received dual immunotherapy for up to two years or until disease progression or unacceptable toxicity occurred;

Control group (n = 358): Received up to four cycles of chemotherapy and optional pemetrexed maintenance therapy (if eligible) until disease progression or unacceptable toxicity.

The primary endpoint of this trial was overall survival (OS) in the intent-to-treat (ITT) population, and the secondary clinical endpoints included progression-free survival (PFS) and objective response rate (ORR) assessed by a fully blinded independent review committee. Exploratory analyses of this study evaluated efficacy outcomes based on biomarker expression levels.

In the CheckMate -9LA trial, an interim analysis with a minimum follow-up time of 8.1 months for OS showed:

Compared with chemotherapy alone, O+Y combined with chemotherapy reduced the risk of death by 31% [hazard ratio (HR): 0.69; confidence interval (CI): 0.55–0.87; p = 0.0006];

The median PFS for combination chemotherapy was 6.8 months, compared with 5.0 months for chemotherapy alone (HR: 0.70; 97.48% CI: 0.57–0.86; p = 0.0001);

Compared with chemotherapy alone, the O+Y combination regimen administered for 2 cycles resulted in a significantly higher ORR: 38% vs. 25% (p=0.0003);

Subsequent analysis showed a sustained improvement in OS with a minimum follow-up of 12.7 months compared to chemotherapy alone (HR: 0.66; 95% CI: 0.55–0.80).

In patients receiving two cycles of O+Y chemotherapy, most observed adverse reactions were mild to moderate. Grade 3 or 4 treatment-related adverse events occurred in 47% of patients. The most common adverse reactions were fatigue (36%), nausea (26%), rash (25%), diarrhea (20%), pruritus (18%), decreased appetite (16%), hypothyroidism (15%), and vomiting (13%).

Reference Source: Bristol Myers Squibb Receives European Commission Approval for Opdivo (nivolumab) plus Yervoy (ipilimumab) with Two Cycles of Chemotherapy for First-Line Treatment of Metastatic Non-Small Cell Lung Cancer