Pembrolizumab Combos Miss Primary Endpoints in Liver, Prostate Cancer Trials

Prostate cancer results
The LEAP-002 study evaluated pembrolizumab plus lenvatinib in patients with uHCC; the KEYNOTE-921 study evaluated pembrolizumab plus docetaxel in patients with mCRPC.

Merck announced results from two phase 3 studies evaluating pembrolizumab (Keytruda®) for the treatment of unresectable hepatocellular carcinoma (uHCC) and metastatic castration-resistant prostate cancer (mCRPC).

The multicenter, randomized, double-blind, active-controlled LEAP-002 study ( Identifier: NCT03713593) compared the efficacy and safety of pembrolizumab plus lenvatinib (Lenvima®) with lenvatinib monotherapy for the first-line treatment of 794 adults with uHCC. Results showed that the study did not meet the coprimary endpoints of overall survival (OS) and progression free survival (PFS). While treatment with the combination trended toward improvement in OS and PFS, these results did not meet statistical significance. 

“Our joint clinical development program for Keytruda plus Lenvima is designed to address unmet needs for some of the most challenging-to-treat types of cancer, like hepatocellular carcinoma,” said Dr Gregory Lubiniecki, Vice President, Global Clinical Development, Merck Research Laboratories. “We remain confident in the potential of this combination based on the body of evidence we’ve seen to date and will continue to investigate its role across multiple types of cancer.”

The randomized, double-blind KEYNOTE-921 study ( Identifier: NCT03834506) compared the efficacy and safety of pembrolizumab plus chemotherapy (docetaxel) and prednisone with placebo plus chemotherapy and prednisone in 1030 adult males with mCRPC who had not received prior chemotherapy but whose disease had progressed on or was intolerant to a next-generation hormonal agent. While trending toward improvement, results showed that the pembrolizumab combination was not associated with significant improvements in OS or radiographic PFS (the coprimary endpoints).

“Results from this study serve as an important reminder that metastatic prostate cancer remains very difficult to treat, and more research is needed,” said Dr Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. “We will continue to advance our clinical development program to evaluate Keytruda-based combinations and novel candidates for patients with this disease.”

According to the Company, data from both trials will be presented at an upcoming medical conference.


  1. Merck and Eisai provide update on phase 3 LEAP-002 trial evaluating Keytruda® (pembrolizumab) plus Lenvima® (lenvatinib) versus Lenvima monotherapy in patients with unresectable hepatocellular carcinoma. News release. Merck and Eisai. Accessed August 3, 2022.
  2. Merck provides update on phase 3 KEYNOTE-921 trial evaluating Keytruda® (pembrolizumab) plus chemotherapy in patients with metastatic castration-resistant prostate cancer. News release. Merck. Accessed August 3, 2022.