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 12 mos is favorable compared with historical references in the NSCLC second-line setting.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
2182 - Evaluating the prevalence of the expression of PD-L1 in NSCLC specimens with short-duration formalin fixation using IHC 22C3 pharmDx
Presenter: Keiichi Ota
Session: Poster Display session 1
Resources:
Abstract
5255 - [18F]-FDG PET/CT in predicting PD-L1 status in nasopharyngeal carcinoma
Presenter: Liang Zhao
Session: Poster Display session 1
Resources:
Abstract
4910 - Expression of PD-L1 in Chinese Patients with Common Cancers
Presenter: Min Zheng
Session: Poster Display session 1
Resources:
Abstract
4227 - The clearance of EGF by tumor-associated macrophages is suppressed by chemotherapeutic agent cisplatin
Presenter: Irina Larionova
Session: Poster Display session 1
Resources:
Abstract
5222 - VHIO-300 and a thousand one nights, a tale of Precision Medicine
Presenter: Ginevra Caratù
Session: Poster Display session 1
Resources:
Abstract
5668 - Matched Whole-Genome Sequencing and Whole-Exome Sequencing with Circulating Tumor DNA (ctDNA) Analysis are complementary modalities in clinical practice
Presenter: Robin Imperial
Session: Poster Display session 1
Resources:
Abstract
5772 - Exploring the role of genes associated with familial cancer syndromes on the development of multiple primary tumors
Presenter: Atanaska Mitkova
Session: Poster Display session 1
Resources:
Abstract
4784 - Doxorubicin resistance: early and advanced tumors can use two different strategies based on initial and profound abnormalities in microRNA expression signature
Presenter: Volodymyr Halytskiy
Session: Poster Display session 1
Resources:
Abstract
3456 - From tumor transcriptomes to underlying cell type proportions to better predict prognosis and response to treatments
Presenter: Yuna Blum
Session: Poster Display session 1
Resources:
Abstract
4976 - Optimization of automated germline DNA extraction from non-tumoral formalin-fixed paraffin embedded (FFPE) tissues
Presenter: Omar Youssef
Session: Poster Display session 1
Resources:
Abstract