Abstract 2041
Background
The RTK AXL is implicated in epithelial-to-mesenchymal transition, negative regulation of anti-tumor immunity and resistance to multiple therapies including CPIs. Bemcentinib 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 PhII trial enrolled 48 advanced lung adenocarcinoma pts with progression on or after 1 prior line of PLT-based chemotherapy. Primary endpoint was ORR according to RECIST 1.1. Additional endpoints included efficacy according to biomarker expression, DCR, PFS, OS and safety. Tumor biopsies were analyzed for AXL by IHC, and PD-L1 expression (22C3 pharmDx). Additional biomarker analysis was also performed.
Results
In May 2019, Cohort A was fully recruited: median age 65 (range 39-82) yrs, 61% male, 76% smokers or ex-smokers. Pts had completed a median of 3 treatment cycles. 15 pts were ongoing. Out of 32 pts with available PD-L1, 17 (53%) had TPS <1%, 13 (41%) had TPS 1-49%, and 2 (6%) had TPS >50%. Out of 33 patients with available AXL IHC, 19 (58%) expressed AXL on their tumors. Among pts who had at least 1 evaluable post-baseline scan: ORR was 10/38 (26%) overall, 6/16 (38%) in AXL positive pts (compared to 2/13 (15%) in AXL negative pts), and 7/30 (23%) in pts with TPS 0-49%. 12-mo OS was 54% overall (2 pts lost to follow up). mOS overall was 12.2 mos (95% CI 6.2 – NR). In pts with AXL positive tumors, mOS was 12.2 mos (2.0 – NR) and in AXL negative 12.7 mos (5.6 – NR). In PD-L1 negative pts, mOS was 12.4 mos (5.6-NR). Most common TRAEs (occurring in > 10% of pts) were transaminase increases (35%), asthenia/fatigue (30%), diarrhea (26%), nausea (13%), anemia (11%), and decreased appetite (11%). All cases of transaminase increase were reversible and resolved. 13 pts (28%) had TRAEs grade > 3, all of which were resolved or resolving at the time of writing. No treatment-related deaths were reported.
Conclusions
The combination of bemcentinib and pembro was well tolerated and showed promising efficacy in previously treated IO-naïve NSCLC pts, particularly in those with AXL positive disease, including PD-L1 negative pts. mOS of > 12 mos is favorable compared with historical references in the NSCLC second-line setting.
Clinical trial identification
NCT03184571.
Editorial acknowledgement
Legal entity responsible for the study
BerGenBio ASA.
Funding
BerGenBio ASA.
Disclosure
J.M. Trigo Perez: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD. E. Felip: Advisory / Consultancy, Speaker Bureau / Expert testimony: AbbVie; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Blueprint Medicines; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Guardant Health; Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen; Advisory / Consultancy, Speaker Bureau / Expert testimony: Medscape; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck KGaA; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Sharp & Dohme; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: Touchtime. A. Helland: Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: PierreFabre; Speaker Bureau / Expert testimony: Pfizer. E. Arriola: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim. R. Garcia Campelo: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche/Genentech; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD Oncology; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim. J. Spicer: Honoraria (institution), Research grant / Funding (institution): AstraZeneca; Honoraria (institution), Research grant / Funding (institution): Bayer; Honoraria (institution), Research grant / Funding (institution): BerGenBio ASA; Honoraria (institution), Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (institution), Research grant / Funding (institution): BMS; Honoraria (institution), Research grant / Funding (institution): Curis; Honoraria (institution), Research grant / Funding (institution): Genmab; Honoraria (institution), Research grant / Funding (institution): Roche; Honoraria (institution), Research grant / Funding (institution): Starpharma; Honoraria (institution), Research grant / Funding (institution): Taiho; Shareholder / Stockholder / Stock options: IGEM Therapeutics. R.J. Holt: Full / Part-time employment: BerGenBio ASA. J.B. Lorens: Leadership role, Research grant / Funding (institution), Shareholder / Stockholder / Stock options, Full / Part-time employment: BerGenBio ASA. M. Shoaib: Advisory / Consultancy, Full / Part-time employment: BerGenBio ASA. A. Siddiqui: Advisory / Consultancy, Full / Part-time employment: BerGenBio ASA. E.V. Schmidt: Full / Part-time employment: Merck Sharp & Dome. M.J. Chisamore: Full / Part-time employment: Merck Sharp & Dome. M.G. Krebs: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy: Achilles Therapeutics; Advisory / Consultancy: Octimet; Advisory / Consultancy: Janssen; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: BerGenBio ASA. All other authors have declared no conflicts of interest.
Resources from the same session
5239 - Treatment patterns and outcomes for patients (pts) with anaplastic lymphoma kinase-positive (ALK+) advanced non-small-cell lung cancer (NSCLC) in US clinical practice
Presenter: Matthew Krebs
Session: Poster Display session 1
Resources:
Abstract
5595 - Is there any prognostic significance in pleural involvement and/or effusion (Ple-I/E) in patients with ALK-positive NSCLC?
Presenter: Saadettin Kilickap
Session: Poster Display session 1
Resources:
Abstract
5840 - Crizotinib in patients with advanced or metastatic ROS1-rearranged lung cancer (EUCROSS): A European phase 2 clinical trial – Updated progression-free survival, overall survival and mechanisms of resistance
Presenter: Sebastian Michels
Session: Poster Display session 1
Resources:
Abstract
1905 - NTRK1-3 Genomic Fusions in Non-Small Cell Lung Cancer (NSCLC) Determined by Comprehensive Genomic Profiling
Presenter: Sai-Hong Ou
Session: Poster Display session 1
Resources:
Abstract
3016 - Preferential expression of the affected MET allele in lung carcinomas with heterozygous MET exon 14 skipping mutations: implications for clinical testing
Presenter: Evgeny Imyanitov
Session: Poster Display session 1
Resources:
Abstract
4120 - Brain metastases, treatment patterns and outcomes in ROS1-positive NSCLC patients from US oncology community centers
Presenter: Matthew G Krebs
Session: Poster Display session 1
Resources:
Abstract
3764 - Patients with metastatic non-small cell lung cancer and targetable molecular alterations in Germany. Treatment and first outcome data from the prospective German Registry Platform CRISP (AIO-TRK-0315)
Presenter: Frank Griesinger
Session: Poster Display session 1
Resources:
Abstract
4070 - Crizotinib vs Platinum-based Chemotherapy as First-line Treatment for Advanced Non-small Cell Lung Cancer with Different ROS1 Fusion Variants
Presenter: Haiyan Xu
Session: Poster Display session 1
Resources:
Abstract
5528 - Genomic and clinical characterization of Non-small cell lung cancer (NSCLC) patients harboring mutations in FGFR2 and FGFR3
Presenter: Matthias Scheffler
Session: Poster Display session 1
Resources:
Abstract
3779 - The expression of HER2-gene polymorphisms -1985G>T and P1170A C>G and their association with the risk of development of lung adenocarcinoma
Presenter: Ivan Aleric
Session: Poster Display session 1
Resources:
Abstract