MSD and Eisai have received a complete response letter (CRL) from the US Food and Drug Administration rejecting accelerated approval of a combination of Keytruda (pembrolizumab) and Lenvima (lenvatinib) for liver cancer.

The companies are developing the combination, which combines an anti-PD-1 therapy and a multiple receptor tyrosine kinase inhibitor, for first-line treatment of patients with unresectable hepatocellular carcinoma (HCC).

Applications for accelerated approval were based on data from the Phase Ib KEYNOTE-524/Study 116 trial, which showed clinically meaningful efficacy in the single-arm setting, including an objective response rate of 36%, with one complete response and 35 partial responses, as well as a median duration of response of 12.6 months.

However, after Roche's Tecentriq/Avastin combination therapy was then approved first for this patient group in the first-line setting, the CRL stated that MSD and Eisai’s applications do not provide evidence that Keytruda in combination with Lenvima represents "a meaningful advantage over available therapies" for the treatment of unresectable or metastatic HCC with no prior systemic therapy for advanced disease.

MSD and Eisai said that since the applications for KEYNOTE-524/Study 116 no longer meet the criteria for accelerated approval, they will now “work with the FDA to take appropriate next steps, which include conducting a well-controlled clinical trial that demonstrates substantial evidence of effectiveness and the clinical benefit of the combination”.

As such, LEAP-002, the Phase III trial evaluating the combination as a first-line treatment for advanced HCC, is currently underway and fully enrolled, the firms noted.