Phase Iii Leap-006 Safety Run-In (Part 1): 1l Pembrolizumab (Pembro) Plus Chemotherapy (Chemo) With Lenvatinib (Len) For Metastatic Nsclc

Pembro + platinum-based chemo is standard 1L therapy for patients (pts) with metastatic NSCLC. In a phase 1b/2 study, pembro + len showed antitumor activity with acceptable safety in multiple tumor types, including metastatic NSCLC treated with ≤2 prior regimens. LEAP-006 (NCT03829319) evaluates 1L pembro + platinum-based chemo ± len in pts with metastatic nonsquamous (nsq) NSCLC. We report the first data from the open-label safety run-in (part 1) of LEAP-006. LEAP-006 is a global, randomized, double-blind, placebo (pbo)-controlled, 2-part, phase 3 study enrolling pts aged ≥18 y with metastatic, treatment-naive nsqNSCLC, ECOG PS 0/1, and tumor sample available for PD-L1 expression; and without actionable genetic aberrations. In part 1, pts received len 8 mg/d + pembro 200 mg + pemetrexed (pem) 500 mg/m2 + carboplatin AUC 5 or cisplatin 75 mg/m2 Q3W in cycles 1‒4; then pembro (up to 31 more cycles) with len + pem until PD/toxicity. Dose-limiting toxicities (DLTs; selected prespecified grade ≥3 AEs or prespecified criteria for thrombocytopenia or any grade thromboembolic event) were assessed for 21 d after first dose. 13 pts were enrolled and treated in part 1 (data cutoff, Mar 3, 2020; median study follow-up, 7.5 [range, 5.7–10.3] mo). Pts received a median of 10 (range, 2–12) cycles of therapy. There were 2 DLTs–both grade 3 hyponatremia in pts receiving cisplatin. 10 pts (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 pts (31%) had grade 3 hypertension; none had grade ≥3 proteinuria. There were no infusion reactions. ORR was 69.2% (95% CI, 38.6-90.9; n = 9; all PR); 3 pts (23.1%) had SD. Of 13 pts, 11 were alive and 10 were progression free by BICR. As <3 DLTs occurred in each platinum-containing arm, enrollment into part 2 began, in which pts randomly receive platinum-based chemo + pembro (similar to part 1) with either len or pbo. Results from part 1 showed acceptable safety and tolerability, and preliminary evidence of antitumor activity with 1L len + pembro + platinum-based chemo in pts with metastatic nsqNSCLC. Enrollment in part 2 is ongoing.