Abstract 986P
Background
METex14 is a driver mutation occurring in 3–4% of NSCLC cases, typically in the absence of other drivers, and is associated with poor prognosis.1Capmatinib is a highly selective and potent MET inhibitor with antitumour activity in previously treated and untreated pts with advanced METex14 NSCLC, including those with CNS disease.2This is the first whole transcriptome analysis in pts treated with capmatinib in GEOMETRY Mono-1 (NCT02414139).
Methods
Pts with advanced METex14 NSCLC received oral capmatinib 400 mg twice daily.2 mRNA from baseline tumour samples was enriched and sequenced. Differences in MET and PD-L1 expression in responders vs non-responders (per central RECIST 1.1) were assessed by t-test. Gene set enrichment analysis was performed adjusting for prior therapy status, estimated tumour purity score and false discovery rate.3 Multivariate regression was performed to associate MET expression and gene expression signatures (GES) with tumour response.
Results
Baseline tumour biopsies from 111 of 160 METex14 NSCLC pts were successfully profiled by RNAseq (41 pts received capmatinib as 1 line [1L], 70 pts as 2 or 3 line [2/3L]). Baseline MET and PD-L1 expression was similar in the 1L and 2/3L pts. High baseline MET expression (above median) was significantly associated with best overall response in 1L pts (nominal p<0.01); pts in 2/3L showed a similar trend (nominal p=0.08). 1L pts with high MET expression had significantly longer PFS than 1L pts with low MET expression (p<0.01, Cox model). PD-L1 expression did not correlate with response. A cell proliferation GES was significantly associated with response but was not an independent predictor of response after accounting for MET expression per multivariate regression.
Conclusions
In a whole transcriptome analysis of baseline METex14 NSCLC tumours from patients treated with capmatinib, higher baseline expression of MET was found to be associated with better response. 1. Socinski et al JCO Precision Oncology 2021; https://doi.org/10.1200/PO.20.00516; 2. Wolf et al NEJM 2020; https://doi.org/10.1056/NEJMoa2002787; 3. Koshihara et al Nat Commun 2013;4:2612.
Clinical trial identification
NCT02414139, first posted 10 April 2015.
Editorial acknowledgement
Olga Ucar of Novartis Pharmaceuticals UK Ltd, London, UK, for providing medical writing assistance.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceuticals Corporation.
Disclosure
J. Wolf: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Blueprint, BMS, Boehringer Ingelheim, Daiichi Sankyo, Ignyta, Janssen, Lilly, Loxo, MSD, Novartis, Pfizer, Roche, Seattle Genetics, Takeda; Financial Interests, Personal, Invited Speaker: Bayer, Chugai; Financial Interests, Institutional, Research Grant: BMS, Janssen, Novartis, Pfizer. H.J.M. Groen: Financial Interests, Institutional, Advisory Role: Eli Lilly; Financial Interests, Institutional, Advisory Board: Novartis. D.S.W. Tan: Financial Interests, Institutional, Research Grant: ACM Biolabs, Amgen, AstraZeneca, Pfizer; Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, C4 Therapeutics, DKSH, GSK, Boehringer Ingelheim, Novartis, Merck, Pfizer, Takeda, Roche. E.B. Garon: Financial Interests, Personal, Advisory Board: Novartis, Merck, BMS, EMD Serono, Regeneron, Sanofi, Natera, Shionogi, ABL Bio, Xilio, GSK, Boehringer Ingelheim, Eisai, Gilead, Eli Lilly, Personalis; Financial Interests, Institutional, Invited Speaker: Novartis, Merck, EMD Serono, Eli Lilly, Genetech, Iovance, Neon, Mirati, AstraZeneca, BMS, ABL Bio; Non-Financial Interests, Advisory Role, Scientific Advisory Board: Lungevity. D. Demanse, A. Robeva, A. Yovine: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. L. Fairchild, A.D. Boran: Financial Interests, Personal, Full or part-time Employment: Novartis. R. Heist: Financial Interests, Personal, Advisory Board: Daichii Sankyo, Novartis, EMD Serono; Financial Interests, Personal, Invited Speaker: Chugai Roche; Financial Interests, Personal, Other, review of cancer histories: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board, consulting honoraria: AbbVie; Financial Interests, Institutional, Invited Speaker: Daichii Sankyo, Novartis, AbbVie, Roche, Incyte, Mirati, Agios, Corvus, Turning Point, Lilly, Exelixis; Non-Financial Interests, Member: IASLC, ASCO, AACR.