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BMS data add to checkpoint inhibitor combo confusion

Opdivo and Yervoy meet one objective but miss another in CheckMate-214

BMSBristol-Myers Squibb has reported mixed results from a trial of its two checkpoint inhibitors - Opdivo and Yervoy - in metastatic renal cell carcinoma (RCC), a form of kidney cancer.

The combination of PD-1 inhibitor Opdivo (nivolumab) and CTLA-4 inhibitor Yervoy (ipilimumab) met one objective in the study but missed another, adding to evidence that trying to harness these two immuno-oncology mechanisms can yield unexpected results.

The CheckMate-214 trial compared Opdivo and Yervoy to Pfizer's targeted RCC therapy Sutent (sunitinib) in patients with previously-untreated RCC. On the plus side, BMS' combo was able to improve the overall response rate (ORR) to 41% compared to 26% with Sutent, which is the standard first-line therapy for RCC.

However, while there was an improvement in progression-free survival (PFS) in Opdivo/Yervoy-treated patients compared to Sutent, 11.6 versus 8.4 months, the difference did not reach statistical significance.

The combination of Opdivo and Yervoy has already shown its worth in melanoma, with BMS claiming approval for the pairing in 2015 on the back of data from the CheckMate-067 trial, and that led to expectations that blocking PD-1 and CTLA-4 together could be a potent therapeutic strategy in cancer immunotherapy.

Fast forward to now, and the hypothesis is starting to look less healthy. Last month, AstraZeneca reported preliminary results from the much-anticipated MYSTIC trial of its PD-L1 inhibitor Imfinzi (durvalumab) and CTLA-4 inhibitor tremelimumab, missing the primary objective of an improvement in PFS. AZ is continuing the trial in the hope that it can demonstrate that the duo will improve overall survival, but the failure on PFS has lowered expectations of a positive outcome.

BMS meanwhile said earlier this year that it wouldn't be able to file for accelerated approval of Opdivo and Yervoy in first-line non-small cell lung cancer (NSCLC), giving few details but leading to speculation that the data was not as robust as hoped. The company is waiting on the results of Opdivo/Yervoy in first-line NSCLC, due in 2019.

Meanwhile, the failure of Opdivo to show a benefit in first-line NSCLC on its own - in contrast to Merck & Co's rival Keytruda (pembrolizumab) - shows that there is a fine line between success and failure in immuno-oncology.

BMS says it is unfazed by the CheckMate-214 results, adding that it is "encouraged by the totality of the data" and will continue the trial to get a read-out on overall survival, its third primary endpoint. And analysts at Bernstein agree with that assessment, suggesting the data could be strong enough for a regulatory filing.

"This is an important study in first-line renal cancer as these patients need new options," commented Vicki Goodman, who heads BMS' development activities in melanoma and genito-urinary cancers.

"The company plans to share these important first-line data with regulatory authorities and we look forward to reporting overall survival when these data mature," she added.

Article by
Phil Taylor

16th August 2017

From: Research

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