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1313P Phase III LEAP-006 safety run-in (Part 1): 1L pembrolizumab (Pembro) + chemotherapy (Chemo) with lenvatinib (Len) for metastatic NSCLC

2020; Elsevier BV; Volume: 31; Linguagem: Inglês

10.1016/j.annonc.2020.08.1627

1569-8041

Makoto Nishio, Nir Peled, Alona Zer, Baerin Houghton, Jair Bar, David Z. Drew, Roy S. Herbst, Delvys Rodríguez‐Abreu, R. Talpur, Lisa Golden, Lei Yin, T. Dang, Rina Hui,

Advanced Breast Cancer Therapies

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.