Bristol-Myers Squibb announced Monday results from the Phase II CheckMate-069 study showing that in patients with previously untreated advanced melanoma, the combination of Opdivo (nivolumab) and Yervoy (ipilimumab) demonstrated superior efficacy compared to Yervoy alone. Michael Giordano, head of oncology development at the company said the "results reinforce our belief that the future lies in the combination of immuno-oncology agents."
The trial randomised 142 previously untreated patients with stage III or IV melanoma to receive treatment with Opdivo plus Yervoy or Yervoy alone. The primary endpoint of the study was the objective response rate in patients with BRAF wild-type tumours, while the secondary endpoints included progression-free survival (PFS) in patients with BRAF wild-type tumours, the objective response rate and PFS in patients with BRAF V600 mutation-positive lesions, as well as safety endpoints.
Data from the trial, which were presented at the American Association for Cancer Research (AACR) annual meeting and published in the NEJM, showed that for the primary endpoint, patients with BRAF wild-type mutation status who received Opdivo plus Yervoy had an objective response rate of 61 percent, versus 11 percent for those given Yervoy alone. Meanwhile, complete responses were reported in 22 percent of patients with BRAF wild-type mutation status administered the combination, compared to no patients who received Yervoy monotherapy.
Compared with Yervoy only-treated patients, the combination regimen reduced the risk of progression in BRAF wild-type and BRAF mutation-positive patients by 62 percent and 60 percent, respectively, while PFS in BRAF wild-type patients in the combination arm was not reached. Meanwhile, in patients with BRAF mutation-positive patients, PFS was 8.5 months for the combination therapy, versus 2.7 months for Yervoy alone.
Additionally, Bristol-Myers Squibb said that the safety profile of the combination regimen was consistent with previous findings. However, the incidence of grade 3 or grade 4 adverse events was 54 percent for the combination treatment, compared with 24 percent for Yervoy monotherapy, while the rates of treatment discontinuation were 47 percent for the Opdivo plus Yervoy regimen versus 17 percent for Yervoy alone.
"These data are unprecedented in advanced melanoma, showing efficacy results that have not previously been observed with immuno-oncology agents," commented F. Stephen Hodi, author of the NEJM paper. "With the Opdivo plus Yervoy regimen, we observed much higher response rates which were sustained, as well as significant reduction in tumour burden than with Yervoy," Hodi added.
Opdivo became the first PD-1 inhibitor available anywhere in the world following its launch in Japan in September 2014. The therapy was later granted accelerated approval by the FDA for the treatment of melanoma, while its indication was expanded last month to include the treatment of advanced squamous non-small-cell lung cancer in select patients.
For related analysis, see ViewPoints: Bristol-Myers Squibb ups the stakes with combination melanoma play, as well as ViewPoints: Can Bristol-Myers Squibb deliver first-line longevity for its Yervoy franchise? See also ViewPoints: First in line – Opdivo and Keytruda make their mark in melanoma, but at what cost to sales of Yervoy?
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