Lenvatinib Plus Pembrolizumab for Patients With Previously Treated Advanced Colorectal Cancer: Results From the Phase II LEAP-005 Study.

BACKGROUND

Current treatments for patients with previously treated metastatic colorectal cancer (CRC) have poor outcomes. LEAP-005 (ClinicalTrials.gov, NCT03797326) was a multicohort, open-label phase II study evaluating the efficacy and safety of lenvatinib plus pembrolizumab in participants with previously treated selected solid tumors. We report findings from the LEAP-005 CRC cohort.

PATIENTS AND

METHODS

Participants aged ≥ 18 years with advanced (metastatic and/or unresectable) CRC with 2 prior lines of systemic therapy were eligible for the CRC cohort of LEAP-005. Participants received oral lenvatinib (20 mg/day) plus intravenous pembrolizumab (200 mg Q3W) combination therapy (Arm 1) or lenvatinib (24 mg/day) monotherapy (Arm 2). Dual primary endpoints were objective response rate (ORR) per RECIST version 1.1 and safety. Secondary endpoints were duration of response (DOR), progression-free survival (PFS), and overall survival (OS).

RESULTS

135 participants were enrolled in the CRC cohort (Arm 1, n = 105; Arm 2, n = 35). In Arm 1, ORR was 14% (95% CI, 8-23), median PFS was 3.4 (95% CI, 2.1-4.1) months, and OS was 8.7 (95% CI, 7.0-10.0) months. In Arm 2, ORR was 7% (95% CI, 1-22), median PFS was 3.4 (95% CI, 2.1-4.2) months, and OS was 7.7 (95% CI, 5.6-14.8) months. Treatment-related AEs occurred in 96% of participants (grade 3/4, 63%) in Arm 1 and 97% (grade 3/4, 63%) in Arm 2. One participant in Arm 1 died due to treatment-related intestinal perforation.

CONCLUSION

Lenvatinib plus pembrolizumab demonstrated antitumor activity in participants with advanced CRC with 2 prior lines of treatment. No new safety signals were identified.