1379P - c-Met protein overexpression and telisotuzumab vedotin efficacy by biopsy age, type, and region in the LUMINOSITY phase II study

Background

c-Met protein (MET protein) is frequently overexpressed in patients (pts) with NSCLC and is associated with poor prognosis. Telisotuzumab vedotin (Teliso-V) is a c-Met–directed antibody-drug conjugate that has shown efficacy in pts with c-Met protein–overexpressing NSCLC. The phase 2 LUMINOSITY trial (NCT03539536), designed to identify pts with pretreated (≤2 prior lines [L]) NSCLC and c-Met protein overexpression (OE) best suited to Teliso-V, has shown durable responses in pts with advanced/metastatic non-squamous EGFR wildtype (NSQ EGFR WT) NSCLC. This analysis aimed to characterize c-Met protein OE and ORR in NSCLC samples from LUMINOSITY.

Methods

Prevalence of c-Met OE was assessed in samples (pre)screened for eligibility for the NSQ EGFR WT cohort. c-Met protein expression was measured by an IHC clinical trial assay for MET (SP44) on archived (before 1L start) or post-progression (after progression on prior L) tumor samples. c-Met positivity (+) was defined at 3+ staining intensity in ≥25% tumor cells (TCs), c-Met intermediate in ≥25% to <50% TCs, and c-Met high in ≥50% TCs. Association between age of biopsy at time of IHC and ORR (confirmed CR + PR) was analyzed in samples with c-Met protein OE from 161 efficacy-evaluable pts.

Results

In total, 1954 samples were analyzed (Europe [EU] n=763, US/Canada [US-C] n=265, Pan-Asia [P-A] n=519, rest of world [ROW] n=407); 1628 (83%) tissues were archived and 326 (17%) post-progression. Overall, 24% (462) of samples were c-Met+ (archived: 22%; post-progression: 32%) and 13% (263) c-Met high (archived: 13%; post-progression: 18%). The prevalence of c-Met+ NSCLC in EU/US-C/P-A/ROW was 21%/25%/30%/20% and of c-Met high 13%/12%/18%/10%. ORR by time of biopsy is shown in the table. Table: 1379P

ORR by age and type of biopsy (baseline or post-progression)

^aAt the time of c-Met protein analysis by IHC.NaN, no observation within the range; ORR, objective response rate: confirmed CR + confirmed PR.

Conclusions

The overall prevalence of c-Met+ NSCLC was 24% and of c-Met high 13%; similar rates were seen across regions or between pre- and post-treatment samples. ORR was not affected by age or type of biopsy.

Clinical trial identification

NCT03539536.

Editorial acknowledgement

Medical writing support was provided by Iratxe Abarrategui, PhD, CMPP, of Aptitude Health, The Hague, the Netherlands, and funded by AbbVie.

Legal entity responsible for the study

AbbVie Inc.

Funding

AbbVie Inc.

Disclosure

J. Bar: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BMS, Causalis, MSD, Merck Serono, Novartis, Roche, Takeda; Financial Interests, Institutional, Research Funding: Immunai, OncoHost, MSD, AstraZeneca. S. Baijal: Financial Interests, Personal, Speaker, Consultant, Advisor, Honoraria: AbbVie, Agilent, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi Sankyo, FoundationOne, Gilead, GSK, Janssen, Lilly, Merck Serono, Merck Sharp & Dome, Novartis, Pierre Fabre, Pfizer, Roche, Servier, Sanofi, Takeda. A. Luo, N. Zhang, C. Ratajczak, P.J. Ansell: Financial Interests, Personal, Full or part-time Employment: AbbVie Inc.; Financial Interests, Personal, Stocks/Shares: AbbVie Inc. S. Lu: Financial Interests, Institutional, Funding, Grants or contract: AstraZeneca; Financial Interests, Institutional, Funding, Grants or contracts: HUTCHMED, Bristol Myers Squibb, Hengrui Medicine, BeiGene, Roche, Hansoh; Financial Interests, Personal, Invited Speaker, Honoraria: AstraZeneca, Hansoh; Financial Interests, Personal, Advisory Role: AstraZeneca, Pfizer, HUTCHMED, Zai Lab, GenomiCare Biotechnology, Yuhan, Menarini, InventisBio Co., Roche; Financial Interests, Personal, Advisory Board, or data safety monitoring board: AstraZeneca, Roche, Mirati Therapeutics. D.R. Camidge: Financial Interests, Personal, Invited Speaker, Honoraria: AbbVie, Amgen, Astellas BioPharma, AnHeart Therapeutics, Apollomics, AstraZeneca, BeiGene, Bio-Thera, Blueprint Medicines, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Elevation Oncology, EMD Serono, GSK, Helsinn Therapeutics, Hengrui Pharmaceutical, Janssen, Kestrel Labs, Lilly, Mersana, Nuvalent Inc., OnKure, Pfizer, Puma Biotechnology, Qilu Pharmaceutical, Ribon Therapeutics, Roche, Sanofi, Seattle Genetics, Takeda, Turning Point Therapeutics; Financial Interests, Institutional, Research Funding: Inivata.