Pembrolizumab Plus Lenvatinib Fails to Meet Expectations in mCRC, Advanced Melanoma

By Rob Dillard - Last Updated: September 15, 2023

The combination of pembrolizumab (KEYTRUDA), an anti-PD-1 therapy, plus lenvatinib (LENVIMA), a multiple-receptor tyrosine kinase inhibitor, failed to meet its primary end point of overall survival (OS) in patients with metastatic colorectal cancer (mCRC) in a recent phase 3 trial. Moreover, the drugs’ manufacturers announced that they discontinued the phase 3 LEAP-003 trial, which was evaluating pembrolizumab plus lenvatinib for the first-line treatment of adults with unresectable or metastatic melanoma because the treatment combination did not demonstrate an improvement in OS.

LEAP-017, a randomized, open-label, phase 3 trial, assessed pembrolizumab plus lenvatinib versus regorafenib or TAS-102 in patients with unresectable mCRC who had received prior treatment.

Researchers analyzed 480 patients with unresectable mCRC that was mismatch repair proficient or not microsatellite instability-high who experienced disease progression on, or became intolerant to, prior therapy. Patients were randomized to receive one of 3 treatment regimens: pembrolizumab 400 mg intravenously on day 1 of each 6-week cycle plus lenvatinib 20 mg orally once daily, regorafenib 160 mg orally once daily on days 1 through 21 of each 4-week cycle, or TAS-102 35 mg/m2 orally twice daily on days 1 through 5 and days 8 through 12 of each 4-week cycle. The findings did not meet statistical significance.

“With the LEAP-003 and LEAP-017 trials, we set out to help improve outcomes for patients with 2 difficult-to-treat advanced cancers, melanoma and colorectal cancer,” said Corina Dutcus, MD, senior vice president, clinical development, oncology at Eisai Inc. in a 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.”

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