Bristol-Myers Squibb's Opdivo, Yervoy combination bests chemotherapy in lung cancer study

Bristol-Myers Squibb announced Monday that a Phase III study investigating the combination of Opdivo (nivolumab) plus Yervoy (ipilimumab) versus chemotherapy in first-line advanced non-small-cell lung cancer (NSCLC) patients whose tumours have high tumour mutation burden (TMB), regardless of PD-L1 expression, met its co-primary endpoint of progression-free survival (PFS). The company added that based on an interim analysis for overall survival (OS), the Data Monitoring Committee recommended that the CheckMate -227 trial continue.

CEO Giovanni Caforio said "we believe these data…are a breakthrough in cancer research and a meaningful step forward in determining which first-line lung cancer patients may benefit most from the combination of Opdivo and Yervoy." Bristol-Myers Squibb noted that the results will be shared with regulatory authorities and presented at a future medical meeting.

In the study, more than 2500 patients have been randomised across non-squamous and squamous histologies, evaluating Opdivo-based regimens versus platinum-doublet chemotherapy in patients with first-line advanced NSCLC. According to Bristol-Myers Squibb, Part 1a of the trial is evaluating Opdivo plus Yervoy and Opdivo monotherapy versus chemotherapy in patients whose tumours express PD-L1. Meanwhile, Part 1b investigated Opdivo plus Yervoy and Opdivo plus chemotherapy versus chemotherapy in patients whose tumours do not express PD-L1. Further, Part 2 of the study is evaluating Opdivo plus chemotherapy versus chemotherapy in a broad population with a primary endpoint of OS.

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Bristol-Myers Squibb noted that the latest results are based on an analysis of patients from the Opdivo plus Yervoy arms and chemotherapy arms across all of Part 1 of the trial. The company indicated that Part 1 has co-primary endpoints for the Opdivo plus Yervoy combination of OS in patients whose tumours express PD-L1 and PFS in patients with high TMB, regardless of PD-L1 expression. According to the drugmaker, approximately 45 percent of the TMB-evaluable patients had tumours that expressed high TMB in the study.

"TMB has emerged as an important biomarker for the activity of immunotherapy," remarked study investigator Matthew Hellmann, adding that the study "showed that TMB is an important, independent predictive biomarker that can identify a population of first-line NSCLC patients who may benefit from the [Opdivo] plus [Yervoy] combination."

Bristol-Myers Squibb entered a collaboration last year with Foundation Medicine to use the latter's genomic profiling and molecular information solutions to identify predictive biomarkers such as TMB in patients enrolled across studies of cancer immunotherapies. Bristol-Myers Squibb said Monday that the companies plan to seek regulatory approval for the FoundationOne CDx as a companion diagnostic to assess TMB for the potential indication of Opdivo plus Yervoy in first-line NSCLC.

In January last year, Bristol-Myers Squibb indicated that it would not pursue an accelerated regulatory pathway for the combination of Opdivo plus Yervoy in first-line NSCLC in the US based on a review of data at the time. Meanwhile, in September, the Phase III CheckMate -214 study evaluating Opdivo plus Yervoy in patients with previously untreated advanced or metastatic renal cell carcinoma was stopped early after results showed that the combination of the PD-1 inhibitor and CTLA-4 inhibitor demonstrated superior OS versus Pfizer's Sutent (sunitinib) in intermediate- and poor-risk patients.  The combination of Opdivo plus Yervoy is currently approved in the US for use in patients with BRAF V600 wild-type unresectable or metastatic melanoma.

For related analysis, read ViewPoints: Bristol-Myers Squibb hedges its bets on a new biomarker in lung cancer.

Separately on Monday, Bristol-Myers Squibb reported fourth-quarter financial results, with sales rising 4 percent year-over-year to $5.4 billion as revenue from Opdivo lifted 4 percent to $1.4 billion, while sales of Yervoy climbed 2 percent to $269 million.

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