Final results from CheckMate -227 part 1 demonstrating superior overall survival for Opdivo + low-dose Yervoy vs. Chemotherapy in advanced non-small cell lung cancer.- BMS

Bristol-Myers Squibb Company announced results from Part 1 of the Phase III CheckMate -227 trial evaluating Opdivo (nivolumab) plus low-dose Yervoy (ipilimumab) as first-line treatment for patients with advanced non-small cell lung cancer (NSCLC). Opdivo plus low-dose Yervoy met the independent co-primary endpoint of overall survival, demonstrating superior benefit compared to chemotherapy in patients whose tumors expressed PD-L1 greater than 1% (Hazard Ratio (HR) 0.79; 97.72% Confidence Interval (CI): 0.65 to 0.96). Additionally, in an exploratory analysis, results showed improved overall survival for patients treated with the combination of Opdivo plus low-dose Yervoy with PD-L1 less then 1% (HR 0.62; 95% CI: 0.48 to 0.78). The two-year survival rate for patients treated with the combination regimen was 40% for both patients whose tumors expressed PD-L1 greater than 1% and patients whose tumors expressed PD-L1 less than 1%. In the chemotherapy control arm, two-year survival rates were 33% and 23%, respectively. These results represent the first and only time a dual Immuno-Oncology (I-O) therapy has demonstrated superior overall survival versus chemotherapy in the first-line NSCLC setting and will be featured in a Presidential Symposium at the European Society for Medical Oncology (ESMO) 2019 Congress in Barcelona, Spain (Presentation #LBA4_PR, Saturday, September 28, 4:30-6:20 PM CEST)

With a minimum follow-up of 29.3 months, patients treated with Opdivo plus low-dose Yervoy, regardless of PD-L1 expression level, experienced a nearly four times longer duration of response compared to patients treated with chemotherapy. In patients with PD-L1 greater than 1%, the objective response rate was 35.9% (95% CI, 31.1 to 40.8) with Opdivo plus low-dose Yervoy (5.8% complete responses) versus 30.0% (95% CI, 25.5 to 34.7) with chemotherapy (1.8% complete responses). The median duration of response (DoR) for the combination therapy arm was 23.2 months versus 6.2 months in the chemotherapy arm. In patients with PD-L1 less than 1%, the objective response rate was 27.3% (95% CI, 30.7 to 45.4) with Opdivo plus low-dose Yervoy (2.1% complete responses) versus 23.1% (95% CI, 17.3 to 29.8) with chemotherapy (1.1% complete responses), with a median DoR of 18 months for the combination therapy arm versus 4.8 months in the chemotherapy arm.

�These positive results validate the immunologic rationale for the dual inhibition of PD-1 and CTLA-4 in the treatment of lung cancer,� said Martin Reck, M.D., Ph.D., CheckMate -227 study investigator, Lung Clinic Grosshansdorf, German Center of Lung Research. �These data show that dual Immuno-Oncology therapy has the potential to deliver deep and durable responses, with a clear survival benefit, in first-line non-small cell lung cancer, without the need for chemotherapy.�

About CheckMate -227 : CheckMate -227 is a multi-part open-label Phase III trial evaluating Opdivo-based regimens versus platinum-doublet chemotherapy in patients with first-line advanced non-small cell lung cancer across non-squamous and squamous tumor histologies: Part 1: Part 1a: Opdivo plus low-dose Yervoy or Opdivo monotherapy versus chemotherapy in patients whose tumors express PD-L1. Part 1b: Opdivo plus low-dose Yervoy or Opdivo plus chemotherapy versus chemotherapy in patients whose tumors do not express PD-L1. Part 2: Opdivo plus chemotherapy versus chemotherapy, regardless of PD-L1. There are two co-primary endpoints in Part 1 for Opdivo plus Yervoy (versus chemotherapy): overall survival (OS) in patients whose tumors express PD-L1 (assessed in patients enrolled in Part 1a) and progression-free survival (PFS) in patients with TMB greater than 10 mut/Mb across the PD-L1 spectrum (assessed in patients enrolled across Parts 1a and 1b). Part 1 met both its co-primary endpoints of PFS with the Opdivo plus Yervoy combination versus chemotherapy in patients whose tumors have high ( greater than 10 mutations/megabase, mut/mb) TMB, regardless of PD-L1 expression, and OS demonstrating a superior benefit for Opdivo plus low-dose Yervoy or Opdivo versus chemotherapy in first-line NSCLC patients whose tumors express PD-L1 greater than 1%. Part 2 did not meet its primary endpoint for OS for Opdivo plus chemotherapy versus chemotherapy alone, in patients with non-squamous NSCLC.