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Merck Halts Phase III Keytruda, Yervoy NSCLC Study

NEW YORK – Merck on Monday said it has decided to halt a Phase III study evaluating the combination of its anti-PD-1 therapy pembrolizumab (Keytruda) with ipilimumab (Bristol Myers Squibb's Yervoy) in first-line, metastatic non-small cell lung cancer patients with high PD-L1 expression and no EGFR or ALK alterations.

The Keynote-598 study is comparing the pembrolizumab-ipilimumab combination against pembrolizumab monotherapy in more than 550 NSCLC patients with PD-L1 expression in at least 50 percent of tumor cells. Merck decided to stop the trial based on the recommendation of an independent data monitoring committee, which determined based on an interim analysis that the risks to patients in the trial outweighed the potential therapeutic benefits. In the study, the combination of two checkpoint inhibitors did not demonstrate any incremental benefit in terms of overall survival or progression-free survival compared to pembrolizumab monotherapy, and these endpoints crossed the futility boundaries.

The company plans to communicate the data from Keynote-598 to regulatory bodies and present it at an upcoming scientific meeting.

In the US, BMS markets the combination of its anti-PD-1 drug nivolumab (Opdivo) and ipilimumab as a first-line treatment for metastatic, NSCLC cancer patients with PD-L1 expression in at least 1 percent of tumor cells and without EGFR or ALK alterations. NSCLC patients can also receive nivolumab with ipilimumab when given with chemotherapy, regardless of their PD-L1 expression status. Nivolumab monotherapy is available for NSCLC patients after they progress on platinum-based chemo.

Merck's competing pembrolizumab is approved as a monotherapy in first-line NSCLC for patients with a PD-L1 tumor proportion score of 1 percent or more and no EGFR or ALK aberrations. Additionally, metastatic NSCLC patients can receive pembrolizumab as a single agent if they have a PD-L1 tumor proportion score of 1 percent or more after they've progressed on platinum-based chemo. The drug can also be combined with chemo for metastatic NSCLC patients as a front-line option.

Merck said it decided to conduct Keynote-598 to specifically explore whether the combination of its anti-PD-1 drug pembrolizumab and ipilimumab would improve outcomes beyond pembrolizumab monotherpay in lung cancer patients. "It is very clear that in this study, the addition of ipilimumab did not add clinical benefit but did add toxicity," Roy Baynes, chief medical officer at Merck Research Laboratories, said in a statement. "[Pembrolizumab] monotherapy remains a standard of care for the treatment of certain patients with metastatic non-small cell lung cancer whose tumors express PD-L1."

Meanwhile, BMS has reported over the past year that in the Phase III CheckMate-915 trial comparing its anti-PD-1 drug nivolumab and ipilimumab against just nivolumab in stage III/IV melanoma, the combination regimen did not significantly improve recurrence-free survival in the all-comer population or in those expressing PD-L1 in less than 1 percent of tumor cells.