Keytruda/Lenvima Trials Stop Due to Lack of Benefit

Two clinical trials investigating Keytruda (pembrolizumab) plus Lenvima (lenvatinib) will be discontinued, as interim analyses showed that they failed to reach main goals, according to a press release from Merck, the manufacturer of Keytruda.

“With the LEAP-003 and LEAP-017 trials, we set out to help improve outcomes for patients with two difficult-to-treat advanced cancers, melanoma and colorectal cancer,” said Dr. Corina Dutcus, senior vice president, clinical development, oncology at Eisai Inc, the manufacturer of Lenvima, in the press release. “While these results are different from our initial expectation, insights from both studies will help contribute to our understanding of Keytruda plus Lenvima. We remain confident in Lenvima as a pillar of Eisai’s oncology portfolio and will continue to evaluate its potential in ongoing trials within the LEAP program.”

The phase 3 LEAP-003 trial evaluating Keytruda (pembrolizumab) plus Lenvima (lenvatinib) for patients with unresectable (not eligible for surgical removal) or metastatic melanoma will be stopped as data from an interim analysis did not show that the drug duo improved overall survival over Keytruda alone.

Overall survival, which is defined as the time during and after treatment until death of any cause, was one of the main goals of the study. The other primary endpoint, progression-free survival (time from treatment until disease worsens or spreads) was met, as an earlier analysis of LEAP-003 showed that there was a significant improvement in the Keytruda/Lenvima group compared to the Keytruda alone group.

The phase 3 LEAP-017 trial will also end. This study was investigating Keytruda plus Lenvima compared to Stivarga (regorafenib) or TAS-102 in patients with unresectable and metastatic colorectal cancer that is mismatch repair proficient or not microsatellite instability-high (MSI-H) whose disease gets worse or stops responding to a prior therapy.

While an analysis of LEAP-017 findings showed that Keytruda plus Lenvima displayed a trend toward improved overall survival, progression-free survival and objective response rate (the percentage of patients whose disease shrinks or disappears from treatment) and duration of response, the difference between the different treatment groups was not statistically significant, meaning that the researchers cannot say for sure that one regimen is superior.

The Keytruda/Lenvima combination has been studied in other malignancies, and one expert even said that the drug duo may become the next standard-of-care treatment for advanced kidney cancer. In September 2022, research showed that Keytruda plus Lenvima led to better outcomes than chemotherapy for patients with pretreated advanced endometrial cancer.

“We are grateful to all the investigators, patients and their families for their participation in these studies, and we will continue to evaluate Keytruda plus Lenvima across different types of cancer where additional treatment options are needed. We remain fully committed to building on existing treatments as part of our efforts to help as many appropriate patients with cancer as we can,” said Dr. Gregory Lubiniecki, Vice President, Global Clinical Development, Merck Research Laboratories, in the press release.

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