Merck pulls the plug on a study evaluating blockbuster Keytruda with Yervoy for NSCLC
About a month ago, upon touting new oncology data, Merck reaffirmed its commitment to exploring new Keytruda combinations for lung cancer patients. The Big Pharma has now pulled the plug on one of those combinations, after interim data showed an increased risk and no reward.
An independent Data Monitoring Committee urged Merck to end a Phase III trial evaluating cash cow Keytruda — which brought in $11.1 billion last year — and Bristol Myers Squibb’s Yervoy (ipilimumab) in PD-L1 positive metastatic non-small cell lung cancer (NSCLC) patients. In an interim analysis, the combination showed no incremental benefit in overall survival (OS) or progression-free survival (PFS), the study’s two primary endpoints.
To make matters worse, the combo was linked to a higher incidence of side effects, including serious adverse events and adverse events leading to “discontinuation or death,” compared to the Keytruda monotherapy, according to Merck.
A total of 568 patients received either 200 mg of Keytruda intravenously once every three weeks for up to 35 cycles and 1 mg/kg IV of Yervoy once every six weeks for up to 18 cycles, or the same amount of Keytruda with a placebo. The full data are coming at a future scientific congress, and will be reported to regulators, the company announced.
“It is very clear that in this study, the addition of ipilimumab did not add clinical benefit but did add toxicity. Keytruda monotherapy remains a standard of care for the treatment of certain patients with metastatic non-small cell lung cancer whose tumors express PD-L1,” Roy Baynes, CMO and head of global clinical development at Merck Research Laboratories, said in a statement.
Bristol Myers Squibb didn’t take the jab lightly, and followed up with Endpoints News to emphasize that its own PD-1, Opdivo, pairs quite well with Yervoy.
“CheckMate -227, CheckMate -9LA and Keynote -598 are all different trials, with different patient populations, comparators, endpoints and durations of follow-up. For example, CheckMate -227 and CheckMate -9LA enrolled patients across PD-L1 expression levels and histologies. Keynote -598 only enrolled patients with PD-L1 expression ≥50%,” a spokesperson said.
While Yervoy has been approved with an anti-PD-1 therapy in some indications, most studies supporting those approvals didn’t compare the combination directly to the anti-PD-1 monotherapy, according to Merck. Back in May, Opdivo and Yervoy got a landmark NSCLC approval approval for PD-L1 positive patients — but the trial compared the combination to treatment with platinum-doublet chemotherapy. Days later, the combo was also approved in combination with a limited course of chemotherapy.
In CheckMate-915, researchers did evaluate Opdivo and Yervoy against Opdivo alone in adjuvant melanoma patients. However, they found that the combination didn’t achieve a significant improvement in recurrence-free survival (RFS) in the all-comer population.
“We remain committed to continued research in melanoma, both to further understand the potential benefit of Yervoy in combination with Opdivo to treat high-risk melanoma patients in the earlier stages of disease, as well as to study additional novel combinations in various settings,” Bristol Myers Squibb VP and head of oncology clinical development Sabine Maier said in a statement at the time.
Keytruda is already approved to treat a variety of cancers aside from NSCLC, including small cell lung cancer, melanoma, head and neck squamous cell cancer, and Hodgkin lymphoma, to name a few. Yervoy is approved for unresectable or metastatic melanoma, and in combination with Opdivo for several cancers, including NSCLC, mismatch repair deficient metastatic colorectal cancer, advanced renal cell carcinoma and hepatocellular carcinoma.
Back in May, Roche’s Tecentriq got FDA approval to treat newly diagnosed, metastatic NSCLC patients without EGFR or ALK mutations whose tumors have high PD-L1 expression. “By virtue of being late to market, Tecentriq monotherapy (IMPOWER110) has little chance of gaining significant share in 1L NSCLC despite posting OS similar to Keytruda in PD-L1 high patients,” Cowen analyst Steve Scala wrote to investors that month.