Aims: Pembrolizumab + platinum-based chemotherapy is standard 1L therapy in metastatic NSCLC, and phase 1b/2 data have shown antitumor activity and acceptable safety with pembrolizumab + lenvatinib in previously treated metastatic NSCLC. The global, randomized, double-blind, placebo-controlled, 2-part, phase 3 LEAP-006 (NCT03829319) study evaluates 1L pembrolizumab + platinum-based chemotherapy ± lenvatinib in metastatic nonsquamous (nsq) NSCLC. We report results from the open-label safety run-in (part-1) of LEAP-006.
Methods: LEAP-006 is enrolling patients ≥18 years with metastatic, treatment-naive nsqNSCLC without actionable genetic aberrations. In part-1, patients received lenvatinib 8 mg/d + pembrolizumab 200 mg + pemetrexed 500 mg/m2 + carboplatin AUC 5 or cisplatin 75 mg/m2 Q3W in cycles 1‒4; then pembrolizumab (up to 31 more cycles) with lenvatinib + pemetrexed until PD/toxicity. Dose-limiting toxicities (DLTs; selected prespecified grade ≥3 AEs or prespecified criteria for thrombocytopenia/any grade thromboembolic event) were assessed days 1‒21.
Results: 13 patients were enrolled and treated in part-1 (data cutoff, 3/3/2020; median follow-up, 7.5 [range, 5.7–10.3] months; median treatment exposure, 10 [range, 2–12] cycles). 2 DLTs occurred–both grade 3 hyponatremia in patients receiving cisplatin. 10 patients (77%) had grade 3–5 AEs (treatment-related, n=7 [54%]), 1 (8%) died due to an AE (not treatment-related), and 6 (46%) had immune-mediated AEs. 4 patients (31%) had grade 3 hypertension; none had grade ≥3 proteinuria. No infusion reactions occurred. ORR was 69.2% (95% CI, 38.6-90.9; n=9; all PR); 3 patients (23.1%) had SD. 11/13 patients were alive; 10 were progression-free by BICR. As <3 DLTs occurred in each platinum-containing arm, part 2 enrollment began, where patients randomly receive platinum-based chemotherapy + pembrolizumab with either lenvatinib or placebo.
Conclusion: Results showed acceptable safety, tolerability, and preliminary evidence of antitumor activity with 1L lenvatinib + pembrolizumab + platinum-based chemotherapy in patients with metastatic nsqNSCLC. Part 2 enrollment is ongoing.