Lenvatinib plus pembrolizumab for patients with previously treated biliary tract cancers in the multicohort phase II LEAP-005 study.

• DOI: 10.1200/jco.2021.39.3_suppl.321
• Publication Date: 2021-01-22T19:59:19Z
• Authors: Luis Villanueva; Zarnie Lwin; Hyun Cheol Chung; Carlos Gomez-Roca; Federico Longo; Eduardo Yanez; Helene Senellart; Mark Doherty; Javier García-Cor...; Andrew Eugene Hen...; Corinne Maurice-Dror; Sanjeev Singh Gill; Tae Won Kim; Daniel Heudobler; Nicolas Penel; Razi Ghori; Peter Kubiak; Fan Jin; Kevin Glen Norwood; Donna Graham
• Keywords: Lenvatinib; Clinical endpoint

321 Background: Second-line treatment options for patients with biliary tract cancers (BTC) are limited. Lenvatinib, an anti-angiogenic multikinase inhibitor, in combination the programmed death-1 immune checkpoint inhibitor pembrolizumab, has demonstrated promising antitumor activity a manageable safety profile select advanced solid tumors. LEAP-005 (NCT03797326) is evaluating efficacy and of lenvatinib plus pembrolizumab previously treated tumors; here we present results from BTC cohort LEAP-005. Methods: In this nonrandomized, open-label, phase II study, eligible were aged ≥18 years histologically or cytologically documented (metastatic and/or unresectable) disease progression after 1 prior line therapy, measurable per RECIST v1.1, ECOG PS 0‒1, tissue sample evaluable PD-L1 expression. Patients received 20 mg once daily 200 Q3W up to 35 cycles (approximately 2 years) until confirmed progression, unacceptable toxicity, withdrawal consent. Treatment could continue beyond experiencing clinical benefit. Primary endpoints ORR (per v1.1 by blinded independent central review) safety. Secondary control rate (DCR; comprising CR, PR, SD), duration response (DOR), PFS, OS. Tumor imaging was performed Q9W initiation 54 weeks, then Q12W week 102, Q24W thereafter. Results: 31 enrolled (ECOG 1, 55%; 84% ex-US). As April 10, 2020, median time first dose data cutoff (DCO) 9.5 months (range, 3.1‒11.9), 16 on at DCO. There 3 (10%) PRs 18 (58%) SDs. 10% (95% CI, 2‒26), DCR 68% 49‒83). Median DOR 5.3 2.1+ 6.2). PFS 6.1 2.1‒6.4). OS 8.6 5.6 NR). Treatment-related AEs occurred 30 (97%), including 15 (48%) who had grade 3‒4 AEs; there no treatment-related deaths. (6%) discontinued due (myocarditis, pyrexia; n = each). The most frequent hypertension (42%), dysphonia (39%), diarrhea (32%), fatigue nausea (32%). 14 (45%) immune-mediated patient (3%) infusion-related reaction. Conclusions: Lenvatinib encouraging toxicity therapy. Based these data, enrollment been expanded 100 patients. Clinical trial information: NCT03797326.