Pembrolizumab Plus Lenvatinib Miss in Phase 3 Melanoma, Colorectal Cancer Trials

Credit: Getty Images.
Keytruda is a programmed death receptor-1-blocking antibody; Lenvima is a kinase inhibitor.

Merck and Eisai announced disappointing results from 2 clinical trials evaluating pembrolizumab (Keytruda®) with lenvatinib (Lenvima®).

According to the Companies, the phase 2 LEAP-003 trial ( Identifier: NCT03820986) evaluating the combination as a first-line treatment for adults with unresectable or metastatic melanoma will be discontinued based on the recommendation of an independent data monitoring committee.

Patients in this trial were randomly assigned to receive pembrolizumab plus lenvatinib or pembrolizumab plus placebo; the dual primary endpoints were overall survival and progression free survival (PFS). While in an earlier analysis, the combination led to statistically significant improvement in PFS vs pembrolizumab alone, the most recent analysis showed it did not result in an improvement in overall survival.

In the phase 3 LEAP-017 trial ( Identifier: NCT04776148), the combination of pembrolizumab and lenvatinib was compared with standard of care (regorafenib or trifluridine and tipiracil hydrochloride) for the treatment of patients with unresectable and metastatic colorectal cancer (mismatch repair proficient or not microsatellite instability-high) who experienced disease progression on, or became intolerant to, prior therapy. The primary endpoint of the trial was overall survival.

Findings from the final pre-specified analysis showed a trend toward improvement in overall survival with pembrolizumab plus lenvatinib, though the results did not meet statistical significance. Similarly, the combination was associated with a trend toward improvement in PFS, objective response rate and duration of response; however, these results were not tested for statistical significance.

The Companies noted that results from both trials will be shared with the scientific community following further evaluation of the data.


Merck and Eisai provide update on phase 3 trials of Keytruda® (pembrolizumab) plus Lenvima® (lenvatinib) in certain patients with advanced melanoma (LEAP-003) and metastatic colorectal cancer (LEAP-017). News release. Merck. April 7, 2023.