Bristol-Myers Squibb's Opdivo, Yervoy combination in melanoma fails to hit co-primary endpoint of late-stage study

Bristol-Myers Squibb reported Wednesday that a Phase III study comparing the combination of the PD-1 inhibitor Opdivo (nivolumab) plus the anti-CTLA-4 antibody Yervoy (ipilimumab), versus Opdivo alone, for the adjuvant treatment of certain patients with resected high-risk melanoma failed to meet one of its co-primary endpoints.

The CheckMate -915 trial enrolled 1943 patients who have undergone complete surgical removal of stage IIIb/c/d or IV melanoma. Participants were randomised to receive Opdivo either alone, which is already an approved standard of care, or Opdivo in combination with Yervoy. Bristol-Myers Squibb noted that patients had no prior anti-cancer treatment for melanoma, except surgery for melanoma and/or adjuvant radiation therapy after neurosurgical resection for central nervous system lesions.

Results showed there was no significant benefit for the co-primary endpoint of recurrence-free survival (RFS) in patients with PD-L1 expression of less than 1%. However, the study will continue unchanged on the advice of the data monitoring committee to assess the other main goal of RFS in the intent-to-treat population.

The company recently announced five-year results from the Phase III CheckMate -067 trial, showing that the first-line combination of Opdivo plus Yervoy "continues to demonstrate improved overall survival" in patients with advanced metastatic melanoma. Data showed that five-year overall survival rates were 52% for the Opdivo plus Yervoy combination, 44% for Opdivo alone and 26% for Yervoy alone.

In 2015, the Opdivo plus Yervoy regimen became the first immuno-oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently authorised in more than 50 countries, including the US and Europe. The combination is also approved for patients with intermediate or poor risk, previously untreated advanced renal cell carcinoma and for certain patients with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer.

Opdivo plus Yervoy is also being tested in other cancers, with Bristol-Myers Squibb recently reporting that the combination achieved the main goal of overall survival in the Phase III CheckMate -9LA trial of patients with first-line advanced non-small-cell lung cancer (NSCLC). Early this year, Bristol-Myers Squibb withdrew its application seeking US approval of Opdivo plus Yervoy to treat first-line advanced NSCLC in patients with high tumour mutational burden.

For related analysis, see ViewPoints: Momentum builds for Opdivo/Yervoy combination in first-line lung cancer.

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