2019 ASCO Annual Meeting!
Session: Lung Cancer—Non-Small Cell Metastatic
Type: Poster Session
Time: Sunday June 2, 8:00 AM to 11:00 AM
Location: Hall A
A phase II study of bemcentinib (BGB324), a first-in-class highly selective AXL inhibitor, with pembrolizumab in pts with advanced NSCLC: OS for stage I and preliminary stage II efficacy.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #421)
J Clin Oncol 37, 2019 (suppl; abstr 9098)
Author(s): Enriqueta Felip, Paal Brunsvig, Nuria Vinolas, Santiago Ponce Aix, Enric Carcereny Costa, Manuel Dómine Gomez, Jose Manuel Trigo Perez, Edurne Arriola, Rosario Garcia Campelo, James F. Spicer, Jonathan Robert Thompson, Ana Laura Ortega Granados, Robert J Holt, Katherine Lorens, James B. Lorens, Muhammad Shoaib, Abdul Siddiqui, Emmett V. Schmidt, Michael Jon Chisamore, Matthew Krebs; Hospital Universitari Vall d'Hebron, Barcelona, Spain; Oslo University Hospital, Oslo, Norway; Hospital Clinic, Barcelona, Spain; Hospital 12 de Octubre, Madrid, Spain; Institut Català d'Oncologia, Hospital Germans Trias i Pujol, Badalona, Spain; Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain; Hospital Virgen de la Victoria, Málaga, Spain; Hospital del Mar, Barcelona, Spain; Medical Oncology Service, University Hospital A Coruña (XXIAC-SERGAS), A Coruña, Spain; King's College London, London, United Kingdom; Medical College of Wisconsin Affiliated Hospitals, Menomonee Falls, WI; Medical Oncology, Complejo Hospitalario de Jaén, Jaén, Spain; BerGenBio ASA, Bergen, Norway; Department of Biomedicine, University of Bergen, Bergen, Norway; BergenBio ASA, Bergen, Norway; Merck & Co., Inc., Kenilworth, NJ; Merck & Co., Inc., Rahway, NJ; The Christie NHS Foundation Trust and The University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom
Background: AXL is an RTK implicated in epithelial-to-mesenchymal transition and as a resistance mechanism to multiple therapies including anti-PD1. Bemcentinib (BGB324) is a first-in-class, oral, highly selective and potent AXL inhibitor which has been demonstrated to enhance anti-PD1 therapy in the pre-clinical setting. Methods: This is a Phase II single-arm, two-Stage study with bemcentinib (200mg/d) and pembrolizumab (200 mg/q3wk) for previously treated, IO naïve pts (n = 48 in total) with Stage IV lung adenocarcinoma. The primary endpoint was ORR according to RECIST 1.1 with pre-defined minimum requirement for 18% RR in the first Stage (n = 24) to proceed to Stage 2. Secondary endpoints included DCR, PFS, OS and safety. Tumour biopsies were analysed for PD-L1 (22C3 pharmDx), AXL, and infiltrating immune cells. Results: Stage 1 completed enrolment in Apr ‘18. As of Feb ‘19, 38 pts (24 and 14 in Stage 1 and 2, respectively) have been dosed with the combination; median age 66 (range 39-79) yr, 59% male, all previously received one prior line of platinum-based chemotherapy or a licensed EGFR/ALK-directed therapy. The most common TRAEs (occurring in > 15% of pts) were transaminase increases (37%), diarrhoea (29%), and asthenia (17%). All cases of transaminase increase were reversible and resolved with concomitant administration of systemic corticosteroids and interruption of study treatments. At time of writing, Stage 1 had met the efficacy threshold to proceed to Stage 2 with continued enrolment. Among 29 pts evaluable for response 7 PRs were reported (24%). For AXL positive pts (10/21 with available biopsies), ORR was 40%. PD-L1 status was known for 5 responders: 4 pts (80%) were PD-L1 negative or weakly positive. In Stage 1, mPFS was 4.0 months (95% CI 1.9 – NR) and 5.9 months in AXL positive pts (n = 10; 3.0 - NR). mOS was not mature. Conclusions: Overall, bemcentinib in combination with pembrolizumab was well tolerated and promising clinical activity was seen, particularly in pts with AXL positive disease. Updated results will be reported at the meeting, incl 12-month OS for Stage 1 and preliminary efficacy of Stage 2. Clinical trial information: NCT03184571