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Lenvatinib plus Pembrolizumab for Patients with Previously Treated Biliary Tract Cancers in the Multicohort Phase 2 LEAP-005 Study

2021 Year in Review: Cholangiocarcinoma — December 17, 2021

Results of the phase 2 LEAP-005 study suggest that lenvatinib plus pembrolizumab shows promising antitumor activity and manageable toxicity in previously treated patients with advanced biliary tract cancers.

The nonrandomized, open-label, multicohort phase 2 LEAP-005 study (ClinicalTrials.gov Identifier: NCT03797326) evaluated the efficacy and safety of the antiangiogenic multikinase inhibitor lenvatinib in combination with the anti–PD-1 immune checkpoint inhibitor pembrolizumab in patients with previously treated advanced solid tumors. Results from the biliary tract cancer (BTC) cohort of LEAP-005 were presented at the 2021 American Society of Clinical Oncology Annual Meeting.

The LEAP-005 study enrolled patients aged ≥18 years with histologically or cytologically documented metastatic and/or unresectable BTCs with disease progression after 1 prior line of therapy, measurable disease per RECIST version 1.1, Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1, and a tissue sample evaluable for PD-L1 expression. Eligible patients received lenvatinib 20 mg once daily plus pembrolizumab 200 mg once every 3 weeks for up to 35 cycles (approximately 2 years), or until confirmed disease progression, unacceptable toxicity, or withdrawal of consent. Treatment with lenvatinib could continue beyond 2 years in patients who were experiencing clinical benefit. Primary end points of the study included overall response rate (ORR) by blinded independent central review and safety. Secondary end points included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Tumor imaging was performed once every 9 weeks from treatment initiation for 54 weeks, then once every 12 weeks to week 102, and once every 24 weeks thereafter. Data cutoff was April 10, 2020.

A total of 31 patients were included in the BTC cohort. The median participant age was 65 years. The majority of patients were female (58%), 55% had an ECOG PS of 1, and 90% had received 1 prior line of therapy. At data cutoff, the ORR was 10%, which included 3 partial responses. The DCR was 68%, including 18 participants with stable disease. The median DOR was 5.3 months (range, 2.1+ to 6.2 months). The median PFS was 6.1 months, and the median OS was 8.6 months.

Treatment-related adverse events (TRAEs) in the safety population (n = 31) were reported in 30 patients (97%), with the most common all-grade TRAEs (≥32%) including hypertension (42%), dysphonia (39%), diarrhea (32%), fatigue (32%), and nausea (32%). Grade 3/4 TRAEs were reported in 15 patients (48%); immune-mediated adverse events occurred in 14 participants (45%). No treatment-related deaths were reported. Overall, 2 (6%) patients discontinued treatment due to TRAEs of myocarditis or pyrexia.

Based on these results, the investigators concluded that the combination of lenvatinib plus pembrolizumab showed promising antitumor activity and manageable toxicity in patients with advanced BTC who had received 1 line of prior therapy. Enrollment in the BTC cohort of the LEAP-005 study thus has been expanded to 100 patients to further define the role played by lenvatinib plus pembrolizumab in the treatment of BTC.

Source: Villanueva L, Lwin Z, Chung HC, et al. Lenvatinib plus pembrolizumab for patients with previously treated biliary tract cancers in the multicohort phase II LEAP-005 study. J Clin Oncol. 2021;39(suppl_3):321-321.

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