Abstract 98P
Background
AXL, a transmembrane receptor tyrosine kinase, is expressed in approximately 70–85% of KRAS-mutated NSCLC constituting approximately 30% of lung adenocarcinomas. AXL expression is associated with poor clinical outcomes and has been shown to drive treatment resistance. Mecbotamab vedotin (Mec-V), a conditionally active biologic anti-AXL antibody-drug conjugate (CAB-AXL-ADC), selectively targets AXL-expressing tumor cells.
Methods
In this phase II, multicenter, open-label study, we evaluated patients (pts) with advanced, treatment-refractory metastatic NSCLC. Eligible pts whose NSCLC tumors expressed AXL were treated on days 1 and 8 of a 3-week cycle or every other week with 1.8 mg/kg Mec-V±nivolumab. An exploratory analysis compared the antitumor activity of Mec-V based upon the presence or absence of KRAS mutations.
Results
Among 113 screened NSCLC pts, 78 with AXL+ stage IV NSCLC received Mec-V (n=59) or Mec-V + nivolumab (n=19). Patients received a median of 3 prior lines of therapy, including 1 pt with a partial response who was previously treated with Sotorasib (G12C inhibitor). AXL was expressed by NSCLC tumors among 19 of 27 (70%) pts with mutated KRAS (mKRAS) NSCLC. High AXL tumoral expression also correlated with RAS variants G12C (82%), G12V (100%), and G12A (75%). Clinical characteristics in treated patients were consistent among pts with KRAS mutation status being the distinguishing factor in differences in observed overall survival (OS). Landmark OS at one year was 58% for pts with mKRAS NSCLC vs. 23% for pts with wildtype (wtKRAS) NSCLC. Similarly, median OS was not yet reached (6.5 months - Not Yet Estimable, ongoing) for pts with mKRAS NSCLC vs. 8.7 (5.8–10.2) months for pts with wtKRAS NSCLC.
Conclusions
Overall survival was meaningfully improved for Mec-V treated pts whose NSCLC expressed mKRAS compared to those with wtKRAS. Anti-tumor activity was seen across 9 unique mKRAS variants, indicating pan-mKRAS activity. Pts with mKRAS NSCLC may benefit from the conditionally active AXL-targeting ADC, potentially due to the elimination of cells expressing the tumor resistant AXL receptor. Further studies are planned.
Clinical trial identification
NCT04681131.
Legal entity responsible for the study
BioAtla, Inc.
Funding
BioAtla, Inc.
Disclosure
K. Reckamp: Financial Interests, Personal, Other, consultant: AstraZeneca, Blueprint, Daiichi Sankyo, Genentech, GSK, Janssen, Lilly, Mirati, Novartis; Financial Interests, Personal, Advisory Board: EMD Soreno; Financial Interests, Institutional, Invited Speaker: Genentech, Blueprint, Calithera, Daiichi Sankyo, Elevation Oncology, Janssen. J. Rotow: Financial Interests, Personal, Advisory Board: AstraZeneca, BioAtla, BMS, Boehringer Ingelheim, Daiichi Sankyo, Genentech, G1 Therapeutics, Gilead, Johnson and Johnson, Jazz, Merus, Novocure, Pfizer, Summit, Takeda; Financial Interests, Personal, Invited Speaker: AstraZeneca, Daiichi Sankyo, Pfizer, Regeneron; Financial Interests, Institutional, Invited Speaker: AbbVie, AstraZeneca, Bicycle Therapeutics, BioAtla, Blueprint Medicines, Daiichi Sankyo, Enliven, EpimAb, Lilly, ORIC, RedCloud, Summit, Black Diamond, Synthekine, ImmunityBio. E. Shum: Financial Interests, Personal, Advisory Board: AstraZeneca, Genentech, Boehringer-Ingelheim, Janssen, Regeneron, Bristol Myers Squibb; Financial Interests, Institutional, Funding: Delfi Diagnostics. D.M. Kowalski: Non-Financial Interests, Personal, Advisory Role: BMS, MSD, Roche, Pfizer, AstraZeneca, MEDISON, Johnson & Johnson, Takeda. J. Zugazagoitia: Financial Interests, Personal, Invited Speaker: Takeda, BMS, AstraZeneca, NanoString, Guardant Health; Financial Interests, Personal, Expert Testimony: Roche, Janssen; Financial Interests, Personal, Advisory Board: Sanofi, BMS, Pfizer, Novartis; Financial Interests, Personal and Institutional, Funding, Research Grant: AstraZeneca, Roche, BMS. C. Gay: Financial Interests, Personal, Invited Speaker: ACHL, AstraZeneca, BeiGene, Daiichi Sankyo, IDEOlogy, IDR, MJH, OncLive, PeerView, PER, Targeted Healthcare; Financial Interests, Personal, Advisory Board: Abdera, Amgen, BMS, Boehringer Ingelheim, G1, Jazz, Monte Rosa, OncoHost, Roche/Genentech; Financial Interests, Personal, Other: Catalyst, Kisoji, STCube. L. Villaruz: Financial Interests, Personal, Advisory Board: Sanofi, Gilead, Johnson and Johnson, EMD Serono, Daiichi Sankyo, AstraZeneca; Financial Interests, Institutional, Invited Speaker: Regeneron, GSK, BioAtla, Beigene, Genentech, Fujifilm, Amgen, Boehringer Ingelheim, Merck. J.J. Nieva: Financial Interests, Personal, Advisory Role: Aadi Biosciences, ANP Technologies, AstraZeneca, BioAtla, G1 Therapeutics, Genentech, Kalivir Mindmed, Naveris, Sanofi; Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Other: Cansera; Financial Interests, Personal, Ownership Interest: Affyimmune, Epic Sciences, Indee Bio, Quantgene, Amgen, Johnson & Johnson, Novartis. J. Fuentes Pradera: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Boehringer Ingelheim, Bristol Myers, Merck Sharp & Dohme, GSK, Pfizer. K. Chen, K. Aysola: Financial Interests, Personal, Full or part-time Employment: BioAtla, Inc. D.R. Camidge: Financial Interests, Personal, Advisory Board: AbbVie, Anheart, Apollomics, AstraZeneca, Daiichii Sankyo, Beigene, Betta, BMS, Ellipses, Gallapagos, Genesis, Gilead, Imagene, Indupro, Janssen, Kestrel, Pfizer, Roche, Sutro, Takeda, Triana; Financial Interests, Personal, Invited Speaker: Eli Lilly. All other authors have declared no conflicts of interest.