1440P - Final top-line results of the BGBC008 phase II, multicenter study of bemcentinib and pembrolizumab (bem+pembro) in second-line (2L) advanced non-squamous (NS) non-small cell lung cancer (NSCLC) (NCT03184571)

Background

Treatment options in 2L metastatic NS NSCLC remain limited with modest outcomes to date. AXL, a receptor tyrosine kinase, mediates resistance to immune- and chemotherapy (CT) and is a poor prognostic biomarker in NSCLC. Bemcentinib (bem), a highly selective oral AXL inhibitor, potentiates the immune-checkpoint inhibitor (ICI) effect in pre-clinical models, providing a strong scientific rationale for the bem+pembro combination in this patient population (PP).

Methods

BGBC008 is a ph2 open-label, single-arm study of bem+pembro in 2L NS NSCLC: ICI-naïve patients (pts) (cohort A), CT-naïve pts (cohort B) and pts with prior CT+ICI (cohort C). Primary endpoint was objective response rate (ORR); secondary endpoints included safety, progression-free survival (PFS) and overall survival (OS). Exploratory analyses assessed PD-L1 (by TPS) and AXL (by H-score) status impact on outcomes.

Results

The study enrolled 99 safety-evaluable pts; median age 65 years (range 39-86); 90 pts were efficacy-evaluable (EE). Most common adverse events were gastrointestinal disorders (G ≤2) in >20% of pts and transient liver enzyme increase (G ≤3) in 10% pts. Median (m) OS and mPFS were 13 and 6.2 months (mths), respectively. AXL status impacted mOS: 14.8 vs 9.9 mths (p=0.029) for AXL >5 vs AXL ≤5, respectively. No difference in mOS (10.6 vs 12.4 mths) or mPFS (6 vs 7 mths) in PD-L1+ (TPS≥1) vs PD-L1- (TPS<1) pts, respectively. The ORR of 11.1% in all EE pts and 21.9% in pts with AXL >5 favourably aligns with therapies in 2L NSCLC. Median OS and mPFS in KRAS mutated (KRAS^MT) (n=20) and KRAS wild-type (KRAS^WT)(n=36) were 14.1 vs 10.0 mths (p=0.49) and 9.8 vs 3.8 mths (p=0.009), respectively. The mOS and mPFS for the PD-L1- (n=6) and PD-L1+ (n=11) KRAS^MT pts were 18 vs 11.4 mths (p=0.017) and 17.3 vs 6.1 mths (p=0.09), respectively.

Conclusions

Bem+pembro was well tolerated and efficacious compared to historical controls. Survival benefit was observed in pts with AXL >5, regardless of prior therapy or PD-L1 status. The promising efficacy signal observed in KRAS^MT pts warrants further validation.

Clinical trial identification

NCT03184571.

Editorial acknowledgement

Legal entity responsible for the study

BerGenBio Ltd.

Funding

BerGenBio.

Disclosure

E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Gilead, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Regeneron, Sanofi, Takeda, Turning Point, Pfizer; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, PeerVoice, Pfizer, Sanofi, Takeda, Touch Oncology, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp & Dohme; Financial Interests, Personal, Member of Board of Directors, Independent member: Grifols; Financial Interests, Institutional, Local PI, Clinical Trial: AstraZeneca AB, AbbVie, Amgen, Bayer Consumer Care AG, BeiGene, Boehringer Ingelheim GmbH, Bristol Myers Squibb International Corporation, Daiichi Sankyo Inc., Exelixis Inc., F. Hoffmann-La Roche Ltd., Genentech Inc., GSK Research and Development Limited, Janssen Cilag International NV, Merck Sharp & Dohme Corp, Merck KGAA, Mirati Therapeutics Inc, Novartis Pharmaceutica SA, Pfizer, Takeda Pharmaceuticals International; Non-Financial Interests, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Member, Member of the Scientific Advisory Committee: CAC Hospital Universitari Parc Taulí. M.G. Krebs: Financial Interests, Personal, Advisory Board: Bayer, Roche, Janssen, Guardant Health; Financial Interests, Personal, Invited Speaker: Roche, Janssen; Financial Interests, Institutional, Advisory Board: AstraZeneca, Seattle Genetics; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Carrick, Janssen, Pyramid Biosciences; Financial Interests, Institutional, Local PI: Blueprint, Astex, Bayer, BerGenBio, Immutep, Novartis, Nurix, Nuvalent, Roche, Seattle Genetics, Turning Point Therapeutics; Financial Interests, Institutional, Research Grant: Roche, Novartis; Other, Travel expenses for congress: Immutep, Janssen; Other, Travel expenses: Roche. E. Arriola: Financial Interests, Personal, Advisory Board: Roche, Boehringer Ingelheim, Lilly; Financial Interests, Personal, Invited Speaker: Takeda, MSD, AstraZeneca, BMS, Thermo Fisher Scientific, Guardant Health, Pfizer; Financial Interests, Personal, Other, Co-founder: Trialing Health; Financial Interests, Institutional, Research Grant: AstraZeneca. L. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AZ, Lilly, PharmaMar, BeiGene, Daiichi, Medscape, Per; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Institutional, Coordinating PI: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme Corp, BMS, Janssen-Cilag International NV, Novartis, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Coordinating PI: Amgen; Financial Interests, Other, Member: AACR, ASCO, ESMO; Financial Interests, Other, Foundation Board Member: AECC; Financial Interests, Other, President.ASEICA( Spanish Association of Cancer Research ): ASEICA; Financial Interests, Other, Foundation president: ONCOSUR; Financial Interests, Other, member: Small Lung Cancer Group. M. Domine Gomez: Other, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, MSD Oncology, Pfizer, Roche , Takeda. M. Chisamore: Financial Interests, Institutional, Full or part-time Employment: Merck & Co. Inc; Financial Interests, Institutional, Stocks/Shares: Merck & Co. Inc. D. Micklem: Financial Interests, Institutional, Full or part-time Employment: BerGenBio. N. McCracken: Financial Interests, Institutional, Full or part-time Employment: BerGenBio. C. Oliva: Financial Interests, Institutional, Full or part-time Employment: BerGenBio. C. Gorcea-Carson: Financial Interests, Institutional, Full or part-time Employment: BerGenBio. J. Spicer: Financial Interests, Institutional, Advisory Board, Compensation to my employer for time providing advice: Lilly, AstraZeneca, BMS, GSK, RS Oncology; Financial Interests, Personal, Stocks/Shares, Co-founder: Epsilogen; Financial Interests, Institutional, Local PI, Reimbursement for treatment of patients in trial: Achilles, Genmab, Roche, Seattle Genetics, Trizell, BergenBio, MSD, Gilead; Financial Interests, Institutional, Coordinating PI, Reimbursement for treatment of patients in trial: Starpharma, BMS, IO Biotech, RS Oncology; Non-Financial Interests, Member of Board of Directors, National strategy board: Experimental Cancer Medicine Centres; Non-Financial Interests, Member of Board of Directors, Steering Committee: British Thoracic Oncology Group; Non-Financial Interests, Advisory Role, Advice on licensing decisions for MHRA: CHM Expert Advisory Group on Oncology & Haematology. All other authors have declared no conflicts of interest.