METPRO: Evaluating prognostic value of c-Met protein overexpression and concurrent biomarker presence

Backgroundc-Met (MET) protein overexpression (OE) is associated with poor prognosis in non-small cell lung cancer (NSCLC) and is being investigated as a therapeutic target and predictive biomarker.MethodsThis ongoing, retrospective, US real-world study assesses c-Met OE by immunohistochemistry (IHC) on archived tissue samples from patients (N=500) with metastatic nonsquamous NSCLC at Caris Life Sciences™ and links patient data to the ConcertAI Real-World Data 360™ (RWD360) database. Patients who had archived tissue samples from up to 24 months prior to study initiation were included. Results are reported as c-Met protein OE positive (≥25% tumor cells at 3+ intensity) and high c-Met protein OE (≥50% at 3+) relative to low/no c-Met protein OE (<25% tumor cells or at <3 intensity). Concurrence of c-Met OE with MET amplification (METAmp), METex14 skipping mutations, and PD-L1 positivity (≥50% staining by IHC) is presented. We report results from an interim analysis (IA).ResultsOf 148 eligible patients, 31 (20.9%) were c-Met protein OE positive. Samples were collected primarily at time of diagnosis, while median archived sample age at MET IHC assessment was 18 months. A total of 144 patients were linkable with RWD360 and included in the IA (29 c-Met OE positive; 115 c-Met OE negative). Median follow-up from first line (1L) start (c-Met OE positive, c-Met OE negative) was 255 and 236 days; median age at 1L start was 71 and 70 years. Among patients assessed for biomarker overlap, the positivity rates (c-Met OE positive [n=31], c-Met OE negative [n=115]) were: METAmp, 3.2% (95% CI: 0.1%–16.7%) and 0.9 % (P=0.38); METEx14 skipping, 12.9% (95% CI: 3.6%–29.8%) and 2.6% (P=0.04); PD-L1 ≥50%, 58.1% (95% CI: 39.1%–75.5%) and 20.9% (P≤0.01). When examining overall survival from 1L therapy start, a greater proportion of patients with high c-Met OE (8/13, 61.5%) had a death event compared with patients with c-Met negative OE (29/75, 38.7%), suggesting negative prognostic value of c-Met protein OE.ConclusionsThe IA outcomes are consistent with high prevalence of c-Met OE relative to other MET aberrations. Completed analysis of the entire cohort (N=500) will characterize the potential negative prognostic value of c-Met OE with longer follow-up.Editorial acknowledgementMedical writing support was provided by Atreju Lackey, PhD, of Fishawack Facilitate Ltd., part of Avalere Health, funded by AbbVie.Legal entity responsible for the studyAbbVie, Inc.FundingAbbVie, Inc.DisclosureX. Le: Financial Interests, Personal, Advisory Role: EMD Serono (Merck KGaA), AstraZeneca, Spectrum Pharmaceuticals, Eli Lilly, Boehringer Ingelheim, Bristol Myers Squibb, Novartis, Hengrui Therapeutics, Daiichi Sankyo, and Celgene; Financial Interests, Personal, Research Funding: from Eli Lilly and Boehringer Ingelheim. C. Aggarwal: Financial Interests, Institutional, Research Funding: AstraZeneca, Genentech, Incyte, Macrogenics, Merck Sharp & Dohme, and MedImmune; Financial Interests, Personal, Advisory Role: Genentech, Lilly, Celgene Merck, AstraZeneca, Blueprint Genetics, Shionogi, Daiichi Sankyo/Astra Zeneca, Regeneron/Sanofi, Eisai, BeiGene, Turning Point, Pfizer, Janssen, Boehringer Ingelheim. A. Simmons, S.A. Crawford, S. Ng, C. Chen, S. Karve, S. Stein, K. Woll, P.J. Ansell, A. Mistry: Financial Interests, Personal, Full or part-time Employment: AbbVie, Inc. D. Bryant: Financial Interests, Full or part-time Employment: Caris Life Sciences. I.I. Wistuba: Financial Interests, Personal, Advisory Role: AstraZeneca/MedImmune, Asuragen, Bayer, Bristol Myers Squibb, Genentech/Roche, GSK, Guardant Health, HTG Molecular Diagnostics, Merck, MSD Oncology, OncoCyte, Novartis, Flame Inc., and Pfizer; Financial Interests, Personal, Research Grant: Asuragen, Genentech/Roche, Bristol Myers Squibb, AstraZeneca/MedImmune, HTG Molecular, Merck, and Guardant Health; Financial Interests, Personal, Funding: GSK and Oncocyte, Daiichi Sankyo, Roche, AstraZeneca, Pfizer and Bayer; Financial Interests, Institutional, Research Funding: 4D Molecular Therapeutics, Adaptimmune, Adaptive Biotechnologies, Akoya Biosciences, Amgen, Bayer, EMD Serono, Genentech, Guardant Health, HTG Molecular Diagnostics, Iovance Biotherapeutics, Johnson & Johnson, Karus Therapeutics, MedImmune, Merck, Novarti.