18P - Telisotuzumab vedotin monotherapy in patients with previously treated c-Met protein–overexpressing nonsquamous EGFR wildtype advanced NSCLC: Updated analysis of the LUMINOSITY trial

Background

Telisotuzumab vedotin (Teliso-V) is a c-Met–directed antibody-drug conjugate comprising the monoclonal antibody telisotuzumab and the microtubule polymerization inhibitor monomethyl auristatin E. In the phase LUMINOSITY trial (NCT03539536), Teliso-V monotherapy 1.9 mg/kg showed durable responses and a generally manageable safety in patients (pts) with c-Met protein–overexpressing (OE), EGFR wildtype (WT), non-squamous (NSQ) NSCLC at the primary analysis (J Clin Oncol 2024;42:3000–11). Herein, we present an updated analysis in this population.

Methods

Pts (≥18 years) with locally advanced/metastatic c-Met protein OE NSQ EGFR WT NSCLC and ≤2 prior lines of therapy including ≤1 line of chemotherapy were treated with 1.9 mg/kg Teliso-V every 2 weeks. c-Met protein overexpression (clinical trial assay for MET [SP44] [Roche]) was defined as ≥25% tumor cells with 3+ staining intensity (c-Met high: ≥50% 3+; c-Met intermediate [int]: 25 to

Results

As of Feb 21, 2024, 172 pts received ≥1 dose of Teliso-V; 168 pts (c-Met high, n=84; c-Met int, n=84) were included in the efficacy analyses. Median follow-up was 24.9 mo. Efficacy data are presented in the table. ORR was 34.5% (c-Met high), 23.8% (c-Met int), and 29.2% (c-Met OE total). Most common any-grade treatment-related adverse events (TRAEs) were peripheral sensory neuropathy (31%), peripheral edema (16%), and fatigue (14%). The most common grade ≥3 TRAE was peripheral sensory neuropathy (7%).

Conclusions

In this updated analysis, Teliso-V monotherapy 1.9 mg/kg in pts with c-Met protein OE EGFR WT NSQ NSCLC continued to demonstrate durable responses, with an enrichment in the c-Met–high population. No new safety signals were observed.

Efficacy endpoints

DOR, duration of response; OS, overall survival; PFS, progression-free survival.

^aPer independent central review.

Clinical trial identification

NCT03539536.

Editorial acknowledgement

Medical writing support was provided by Joanne Franklin, PhD, CMPP, from Aptitude Health, The Hague, the Netherlands, and funded by AbbVie.

Legal entity responsible for the study

AbbVie Inc.

Funding

AbbVie Inc.

Disclosure

N. Girard: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Regeneron, AbbVie, Amgen, Lilly, Takeda, Owkin, Leo Pharma, Daiichi Sankyo, Ipsen, Pierre Fabre, Beigene; Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Pfizer, Amgen, MSD, Sanofi, Gilead, Janssen; Financial Interests, Personal, Officer: edimark; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS, Leo Pharma; Financial Interests, Institutional, Research Grant: MSD; Other, Personal, Other, Family member is an employee: AstraZeneca. D.R. Camidge: Financial Interests, Personal, Invited Speaker: AbbVie, Amgen, Astellas BioPharma, AnHeart Therapeutics, Apollomics, AstraZeneca, BeiGene, Bio-Thera, Blueprint, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Elevation Oncology, EMD Serono, GSK, Helsinn Therapeutics, Hengrui Pharmaceuticals, 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 Grant: Inivata. J. Bar: Financial Interests, Personal, Advisory Board: MSD, Takeda, Roche, Pfizer, AbbVie, Bayer, AstraZeneca, Merck Serono, J-C healthcare, Medison Pharma, Amgen, NectinTx; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Other, Steering committee: AbbVie, Merck Healthcare KGaA, Roche, AstraZeneca; Financial Interests, Institutional, Invited Speaker: MSD, Roche, Takeda, AbbVie; Financial Interests, Institutional, Other, local sub-investigator: Novartis; Financial Interests, Institutional, Research Grant: OncoHost, ImmuneAI, AstraZeneca; Non-Financial Interests, Personal, Other, Committee member: IASLC. H. Horinouchi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Eli Lilly, BMS/ONO, Merck Sharp & Dohme, Roche/Chugai, Novartis, Pfizer, Boehringer Ingelheim, Kyowa-Kirin, Nihon Kayaku, AbbVie, Roche/Chugai; Financial Interests, Personal, Advisory Board: AstraZeneca, Eli Lilly, BMS/ONO, Merck Sharp & Dohme, Roche/Chugai, Amgen, Nihon Kayaku; Financial Interests, Institutional, Research Grant: Roche/Chugai, Merck Sharp & Dohme, Daiichi Sankyo, ONO pharmaceutical, AstraZeneca; Financial Interests, Institutional, Invited Speaker: AbbVie. J.W. Goldman: Financial Interests, Personal, Advisory Role: AstraZeneca, Bristol Myers Squibb, Lilly, Pfizer, AbbVie, Genentech; Financial Interests, Institutional, Research Grant: Lilly, Genentech/Roch, Bristol Myers Squibb, AstraZeneca/MedImmune, AbbVie, Corvus Pharmaceuticals, Spectrum Pharmaceuticals, Advaxis; Financial Interests, Personal, Other, Travel, accommodation, expenses: AstraZeneca. N. Daaboul: Financial Interests, Personal, Advisory Role: AstraZeneca, BMS, Eisai, Merck, Pfizer, Novartis, Roche, Taiho, Takeda. I. Cicin: Financial Interests, Institutional, Invited Speaker: Eli Lilly, Roche, MSD, Sanofi, Pfizer, ICON, Janssen, Takeda, Paraxel, Gliead, Novartis, Astra, Jounce, Exelis, Servier; Financial Interests, Personal, Invited Speaker: Yuhan; Other, Personal, Other, Principal investigator for Jounce Therapeutic: Jounce Therapeutic. A. Zer: Financial Interests, Personal, Invited Speaker: Roche, MSD, Takeda, Pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Other, Safety Review Committee Member: Beyond Air; Financial Interests, Personal, Other, Consulting: Gilead; Financial Interests, Personal, Stocks/Shares: Nixio; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Invited Speaker: MSD, AbbVie, Gilead, AstraZeneca. T. Ciuleanu: Financial Interests, Institutional, Other, Principal Investigator: Jounce Therapeutics; Financial Interests, Personal, Other, speaker, consultancy, advisory board, principal investigator: Roche, Merck Sharp Dohme, AstraZeneca, Pfizer, BristolMyersSquibb, Eli Lilly, Amgen, Astellas, Novartis, Takeda; Financial Interests, Personal, Other, speaker, consultancy, advisory board: Janssen, Sandoz, Sanofi, Accord, MagnaPharm; Financial Interests, Personal, Other, Principal Investigator: Tesaro, Mirati, AbbVie, Celltrion; Financial Interests, Personal, Other, Principal Investigatgor: BeiGene. N. Reinmuth: Financial Interests, Personal, Invited Speaker, including Ad-Boards: AstraZeneca; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Hoffmann-La Roche, Lilly, Pfizer, Takeda, Merck, GSK; Financial Interests, Personal, Invited Speaker, including Advisory Boards: Bristol Myers Squibb, Boehringer Ingelheim, MSD; Financial Interests, Institutional, Invited Speaker: Sanofi. D. Planchard: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Samsung, Celgene, AbbVie, Daiichi Sankyo, Janssen, Seagen, Gilead, Pierre Fabre; Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Pfizer, priME Oncology, Peer CME, Samsung, AbbVie, Janssen, Gilead, Seagen; Non-Financial Interests, Personal, Principal Investigator, Institutional financial interests: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Daiichi Sankyo, Sanofi-Aventis, Pierre Fabre, AbbVie, Sanofi, Janssen. A.S. Mansfield: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Advisory Role: Genentech, BMS, AbbVie, AstraZeneca, Janssen, BeiGene, Takeda, Genzyme, Gilead Sciences, Johnson & Johnson Global Services; Financial Interests, Institutional, Speaker’s Bureau: Chugai/Roche; Financial Interests, Institutional, Research Grant: Novartis, Verily, BMS; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: AbbVie, Roche; Financial Interests, Personal, Other: Mesothelioma Applied Reserach Foundation. S. Baijal: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, Boehringer Ingelheim, Chugai, GSK, Janssen, Merck Sharp & Dohme, PierreFabre, Pfizer, Roche, Servier, Sanofi, Takeda; Financial Interests, Personal, Invited Speaker: Agilent, Amgen, Bristol Myers-Squibb, Daiichi Sankyo, FoundationOne, Gilead, Lilly, Merck Serono, Novartis; Financial Interests, Institutional, Invited Speaker: AbbVie, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, GSK, Merck Serono, Merck Sharp & Dohme, Pfizer, Pfizer, Roche. N. Zhang: Financial Interests, Personal, Full or part-time Employment: AbbVie Inc.; Financial Interests, Personal, Stocks/Shares, may own stock: AbbVie Inc. S. Patel: Financial Interests, Personal, Full or part-time Employment: AbbVie; Financial Interests, Personal, Stocks/Shares, may own stock: AbbVie Inc. M.S. Xia: Financial Interests, Personal, Full or part-time Employment: AbbVie Inc.; Financial Interests, Personal, Stocks/Shares, may own stock: AbbVie Inc. C. Ratajczak: Financial Interests, Personal, Full or part-time Employment: AbbVie Inc.; Financial Interests, Personal, Stocks/Shares, may own stock: AbbVie Inc. S. Lu: Financial Interests, Institutional, Research Grant: AstraZeneca, HUTCHMED, Bristol Myers Squibb, Hengrui Medicine, BeiGene, Roche, and Hansoh; Financial Interests, Personal, Invited Speaker: AstraZeneca and Hansoh; Financial Interests, Personal, Advisory Role: AstraZeneca, Pfizer, HUTCHMED, Zai Lab, GenomiCare Biotechnology (Shanghai), Yuhan, Menarini, InventisBio Co., and Roche; Financial Interests, Personal, Other, Data safety monitoring board or advisory board participation: AstraZeneca, Roche, and Mirati Therapeutics. All other authors have declared no conflicts of interest.