e-Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2020

Phase 3 LEAP-006 Safety Run-In (Part 1): 1L Pembrolizumab + Chemotherapy With Lenvatinib for Metastatic NSCLC (#231)

Baerin Houghton 1 , Makoto Nishio 2 , Nir Peled 3 , Alona Zer 4 , Jair Bar 5 , David Drew 6 , Roy S Herbst 7 , Delvys Rodríguez-Abreu 8 , Rakhshandra Talpur 9 , Lisa Golden 10 , Lina Yin 10 , Thao Dang 10 , Rina Hui 11
  1. Mid North Coast Cancer Institute, Port Macquarie, NSW, Australia
  2. Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
  3. Soroka Cancer Center, Ben Gurion University, Be'er Sheva, Israel
  4. Rabin Medical Center, Petah Tikva, Israel
  5. Sheba Medical Center, Tel HaShomer, Ramat Gan, Israel
  6. Holy Cross Medical Group, Fort Lauderdale, Florida, United States of America
  7. Department of Medical Oncology, Yale University School of Medicine, Yale Comprehensive Cancer Center, New Haven, Connecticut, United States of America
  8. Hospital Universitario Insular de Gran Canaria, Las Palmas de Gran Canaria, Spain
  9. Eisai Inc., Woodcliff Lake, New Jersey, United States of America
  10. Merck & Co., Inc., Kenilworth, New Jersey, United States of America
  11. Westmead Hospital and the University of Sydney, Sydney, NSW, Australia

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.