Abstract 78TiP
Background
The combination of platinum chemotherapy, pemetrexed and pembrolizumab (CIT) has become a standard of care as first-line (1L) treatment in patients with non-squamous NSCLC. Despite improvements in response rates and survival, the emergence of primary or acquired resistance limits its efficacy. Serine/threonine kinase 11 mutations (STK11m) are common (˜20%) in NSCLC and promote immune suppression by activation of AXL signalling. Bemcentinib (BEM), a selective AXL inhibitor, has been shown in preclinical studies to sensitize STK11m NSCLC to pembrolizumab. Therefore, the addition of BEM to CIT has the potential to improve the 1L treatment outcomes of NSCLC, particularly in tumors harboring STK11m.
Trial design
This is an open-label, multi-center, phase Ib/IIa clinical study to assess the safety, tolerability, and preliminary anti-tumor activity of BEM in combination with CIT as 1L treatment in patients with advanced (stage IIIb/IIIc) or metastatic (stage IV) non-squamous NSCLC without actionable mutations. In the phase IIa, patients with a STK11 mutation will be enrolled. All patients will receive BEM orally on Day 1 of each 21-day CIT treatment cycle. After the completion of 4 cycles of CIT + BEM, patients will receive maintenance with BEM + pemetrexed + pembrolizumab. Phase Ib follows a 3+3 design. Patients will receive BEM + CIT at one of 3 daily BEM dose levels: Cohort 1 = 75 mg; Cohort 2 = 100 mg; or Cohort 3 = 150 mg. An independent data safety monitoring board will review the safety data from each cohort at the end of the dose-limiting toxicity assessment period (the first 21 days of cycle 1 for each patient of each cohort) and will recommend the BEM dose for the phase IIa expansion. The study consists of a screening period (up to 28 days), a treatment period (up to 24 months) and overall survival follow up for each subject for at least 2 years. Up to 24 and 40 patients will be enrolled in the phase Ib and IIa, respectively. The trial is currently enrolling patients in the phase Ib in the US; patients’ recruitment for the phase IIa is planned to open in Q2 2023 in Europe, UK, and US.
Clinical trial identification
EudraCT 2019‐003806‐28/NA/124645.
Legal entity responsible for the study
BerGenBio Ltd, UK.
Funding
BerGenBio.
Disclosure
R. Veluswamy: Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb, AstraZeneca, Merck, Boehringer Ingelheim, BerGenBio, Merus, Novocure, G1 Therapeutics, Regeneron; Financial Interests, Personal, Other, Steering Committee: Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Other, consulting honorarium: BeiGene; Non-Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb, Onconova,, AstraZeneca, Boehringer Ingelheim, Lung Cancer Research Foundation, Stand Up 2 Cancer. S. Bhalla: Financial Interests, Personal, Advisory Board: Takeda. R. Mehra: Non-Financial Interests, Personal, Advisory Board: AstraZeneca; Non-Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Personal, Advisory Board: Rakuten Medical, Coherus, Janssen. M.C. Garassino: Financial Interests, Personal, Advisory Board: AstraZeneca, MDS International GmBH, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Ignyta, Incyte, Inivata, MedImmune, Novartis, Pfizer, Roche, Takeda, Seattle Genetics, Mirati, Daiichi Sankyo, Regeneron, Merck, Ose Immuno Therapeutics, Blueprint, Janssen, Sanofi; Financial Interests, Institutional, Invited Speaker: Eli Lilly, MDS, Pfizer, AstraZeneca, MDS International GmBH, BMS, Boehringer Ingelheim Italia S.p.A., Celgene, Eli Lilly, Ignyta, Incyte, MedImmune, Novartis, Pfizer, Roche, Takeda, Tiziana, Foundation Medicine, GSK, Spectrum Pharmaceuticals; Other, Institutional, Other: AIRC, AIFA, Italian MoH, TRANSCAN, research fundings, Horizon 2020. C. Oliva: Financial Interests, Institutional, Full or part-time Employment: BerGenBio. C. Gorcea-Carson: Financial Interests, Institutional, Full or part-time Employment: BerGenBio. N. McCracken: Financial Interests, Institutional, Full or part-time Employment: BerGenBio. All other authors have declared no conflicts of interest.