1303P - METPRO: Evaluating prognostic value of c-Met protein overexpression and concurrent biomarker presence

Background

c-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.

Methods

This 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).

Results

Of 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.

Conclusions

The 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.

Clinical trial identification

Editorial acknowledgement

Medical writing support was provided by Atreju Lackey, PhD, of Fishawack Facilitate Ltd., part of Avalere Health, funded by AbbVie.

Legal entity responsible for the study

AbbVie, Inc.

Funding

AbbVie, Inc.

Disclosure

X. 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.