The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors

Abstract

Tumor progression and immune evasion result from multiple oncogenic and immunosuppressive signals within the tumor microenvironment. The combined blockade of VEGF and inhibitory immune checkpoint signaling has been shown to enhance immune activation and tumor destruction in preclinical models. The LEAP clinical trial program is evaluating the safety and efficacy of lenvatinib (a multikinase inhibitor) plus pembrolizumab (a PD-1 inhibitor) across several solid tumor types. Preliminary results from ongoing trials demonstrate robust antitumor activity and durable responses across diverse tumor types with a manageable safety profile. Thus, lenvatinib plus pembrolizumab is anticipated to be an important potential new regimen for several solid cancers that currently have limited therapeutic options.

Clinical trial registration: NCT03884101 , NCT03713593 , NCT03820986 , NCT03776136 , NCT03797326 , NCT03829319 , NCT03829332 , NCT03976375 , NCT04428151 , NCT04199104 , NCT03898180 , NCT04246177 (ClinicalTrials.gov).

Abstract

Lay abstract

Over the last 20 years, several new drugs have been developed that have greatly improved outcomes for patients with cancer. However, some patients have tumors that do not respond or become unresponsive to treatment over time when a given drug is used as the sole treatment. To overcome this problem, combinations of drugs that attack the tumor in different ways are being studied. Here, we describe the rationale and design of the LEAP clinical trial program, which is investigating the combination of pembrolizumab and lenvatinib in patients with several solid tumor types who currently have limited available therapies. Pembrolizumab works with the patient’s immune system to attack cancer cells whereas lenvatinib targets angiogenesis, a process that promotes tumor growth by suppling nutrients and oxygen. In early phase trials, the combination of pembrolizumab and lenvatinib has been shown to provide robust antitumor activity, durable responses and manageable safety.