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LEAP-005 Clinical Trial Yields Promising Efficacy and Safety Data for Patients with Gastric Cancer

2021 Year in Review - Gastrointestinal Cancer

Recently released positive findings from the LEAP-005 trial of lenvatinib plus pembrolizumab in the treatment of previously treated gastric cancer leads to cohort expansion.

The LEAP clinical trial program is investigating the efficacy and safety of lenvatinib and pembrolizumab in a broad range of solid tumor types, including advanced gastric cancer. Lenvatinib is an oral multikinase inhibitor that inhibits the angiogenesis necessary for tumor proliferation.1 Pembrolizumab is an intravenously administered PD-1 inhibitor.1 This combination, which targets multiple signaling pathways, is expected to help overcome innate and acquired resistance to antitumor medication.1 In the LEAP-005 phase 2 multicohort open-label study, the combination had antitumor activity with a manageable safety profile. At the 2021 American Society of Clinical Oncology Annual Meeting, Chung and colleagues presented findings from the LEAP-005 gastric cancer cohort, which consisted of 31 patients ≥18 years of age. Patients <65 years of age comprised 58% of the cohort and 87% of the participants were male. The study’s primary end points were objective response rate (ORR) and safety, with secondary end points of duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).

To be eligible for the study, patients had to have confirmed metastatic and/or unresectable gastric cancer with measurable disease per Response Evaluation Criteria in Solid Tumors v1.1, an Eastern Cooperative Oncology Group performance status of 0 to 1, and received ≥2 previous lines of treatment. Tissue samples were provided by each patient and tested for PD-L1. From these samples it was discovered that 71% of the patients had a PD-L1 combined positive score ≥1. Tumor imaging was performed every 9 weeks after starting treatment and continued every 9 weeks for 54 weeks. At this point, imaging was performed every 12 weeks to week 102, then every 24 weeks.

Participants received 20 mg lenvatinib once a day and 200 mg pembrolizumab every 3 weeks. Lenvatinib treatment could continue beyond 2 years if the participant derived clinical benefit from the treatment. Pembrolizumab treatment continued for up to 35 cycles. Treatment continued until there was confirmed disease progression, the participant experienced unacceptable toxicity, or the participant withdrew consent. The median time from the first treatment dose to data cutoff was 7 months. At this time, 19 patients had discontinued treatment. The ORR was 10%, DCR was 48%, and median DOR was not reached. A complete response was seen in 1 patient, 2 patients had a partial response, and 12 patients had stable disease. Median PFS was 2.5 months and median OS was 5.9 months.

Adverse events (AEs) were experienced by 28 patients, with 13 patients experiencing grade 3 to grade 5 AEs. Hemorrhage, a treatment-related AE, led to the death of 1 patient. Although there were no infusion-related reactions, 8 patients had immune-mediated AEs: 5 developed hypothyroidism, 2 developed hyperthyroidism, and 1 developed pneumonitis.

Based on the acceptable safety profile and antitumor activity, enrollment in this cohort was expanded to 100 patients.

Source: Chung HC, Lwin Z, Gomez-Roca C, et al. LEAP-005: a phase 2 multicohort study of lenvatinib plus pembrolizumab in patients with previously treated selected solid tumors—results from the gastric cancer cohort. J Clin Oncol. 2021;39(suppl_3):230-230.


  1. Taylor MH, Schmidt EV, Dutcus C, et al. The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. Future Oncol. 2021;17:637-648.
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