Merck and Eisai have reported mixed-bag results from the Phase 3 LEAP-010 trial for KEYTRUDA (pembrolizumab) plus LENVIMA (lenvatinib) in a type of head and neck squamous cell carcinoma (HNSCC).

According to the parties, two planned interim analyses were undertaken over a period of 11 months by an independent data monitoring committee (DMC).

The primary endpoints of the late-stage clinical trial were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).

The first analysis saw KEYTRUDA plus LENVIMA deliver a statistically substantial improvement in PFS and ORR versus KEYTRUDA plus placebo.

As per the second analysis, the investigational combination did not show an improvement in OS in comparison to KEYTRUDA plus placebo.

Merck and Eisai assessed the probability of achieving the protocol-specified threshold for statistical significance for OS and determined it to be low.

The safety profile of KEYTRUDA plus LENVIMA was on par with previously reported observations on the combination.

Eisai global clinical development, oncology senior vice president Corina Dutcus said: “While we were initially encouraged to see that KEYTRUDA plus LENVIMA met two of its three primary endpoints at an earlier interim analysis, unfortunately the combination did not meet the threshold for the third primary endpoint of overall survival.

“Our clinical programme is designed to help accelerate our efforts to tackle difficult-to-treat, advanced cancers, and while the outcome may not always be what we anticipate, we know that this is part of clinical development, and we remain committed to scientific exploration in pursuit of improving care for patients.”

The LEAP-010 trial featured patients with recurrent or metastatic HNSCC whose tumours express PD-L1.

KEYTRUDA plus LENVIMA was evaluated as a first-line treatment for the patient population in comparison to KEYTRUDA monotherapy. A total of 511 patients are estimated to have been involved in the randomised, placebo-controlled, double-blinded LEAP-010 clinical trial.

Merck Research Laboratories global clinical development vice president Gregory Lubiniecki said: “With the LEAP-010 trial, we aimed to explore whether this combination could improve upon options already available with KEYTRUDA-based regimens for appropriate patients with metastatic or with unresectable, recurrent HNSCC.

“Although the progression-free survival results from this study were encouraging, unfortunately, the combination did not result in an overall survival benefit for patients. We will apply lessons from this trial to help continue advancing research of this combination.”

KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy from Merck, which has been approved for multiple cancer indications.

LENVIMA, which was discovered by Eisai, is an orally available multiple receptor tyrosine kinase inhibitor (TKI). It is also approved for various indications of cancer.

The combination of KEYTRUDA and LENVIMA is approved for the treatment of advanced renal cell carcinoma (RCC) and some forms of advanced endometrial carcinoma in the US, European Union, and other countries.