1257MO - ABBV-400, a c-Met protein-targeting antibody-drug conjugate (ADC), in patients (Pts) with advanced EGFR wildtype (WT) non-squamous (NSQ) non-small cell lung cancer (NSCLC): Results from a phase I study

Background

c-Met (also known as MET) protein is often overexpressed in NSCLC. ABBV-400 is an ADC composed of the c-Met–targeting mAb telisotuzumab conjugated to a novel topoisomerase 1 inhibitor payload. A phase 1 study (NCT05029882) of ABBV-400 in adults with advanced solid tumors is ongoing; in dose escalation (N=57), ABBV-400 had a tolerable safety profile and promising efficacy. Here, we present dose expansion results from the EGFR WT NSCLC cohort.

Methods

Pts with EGFR WT NSQ NSCLC that had progressed after platinum, ICI, and/or targeted therapy were enrolled. Pts received ABBV-400 at 2.4 (n=39) or 3.0 (n=9) mg/kg Q3W. Primary objectives included ABBV-400 safety, tolerability, PK, and preliminary efficacy. Tumor tissue c-Met protein expression was assessed centrally by IHC.

Results

In total, 48 pts were enrolled in the EGFR WT cohort. Median age was 66 yr (32–85). Median prior therapies was 2 (1–9). Median treatment duration was 3.5 mo (0.7–10.6) and median follow-up was 3.7 mo. TEAEs of any grade (G)/G≥3 occurred in 100%/63% pts, with most common being hematologic (65%) and gastrointestinal (60%). TEAEs of any G in ≥35% of pts were anemia (54%), nausea (42%), decreased appetite (38%), and neutropenia (35%); TEAEs G≥3 in ≥10% of pts were anemia (25%) and neutropenia (15%). The any G unadjudicated interstitial lung disease/pneumonitis rate was 6%. TEAEs leading to discontinuation/reduction occurred in 10%/33% of pts. Efficacy is shown in the table. Preliminary ORR was 44%. Exploratory biomarker analysis is ongoing to establish the association between c-Met protein expression and treatment response. With 30 of 48 pts still on treatment, time-to-event endpoints were not reached.

Conclusions

ABBV-400 has a tolerable safety profile and antitumor activity in pts with NSQ EGFR WT NSCLC, warranting further investigation. Evaluation of ABBV-400 in other NSCLC subtypes is ongoing. Table: 1257MO

Preliminary efficacy^a

^aTime-to-event endpoints (PFS, DOR, OS) are immature.^bConfirmed responses.CBR, clinical benefit rate; CR, complete response; NE, not estimated; NSQ, non-squamous; ORR, objective response rate; PD, progressive disease; PR, partial response; SD, stable disease

Clinical trial identification

NCT05029882.

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

M. De Miguel: Financial Interests, Institutional, Invited Speaker: Janssen, MSD; Non-Financial Interests, Principal Investigator: Janssen, MSD, Roche, PharmaMar, Replimune, Novartis, AbbVie, Achilles, Amunix, Arcus, Furmo, BioNTech, Catalym, Dizal, Genentech, Loxo, Numab, Seagen. N. yamamoto: Financial Interests, Personal, Invited Speaker: ONO, Chugai, Daiichi Sankyo, Eisai; Financial Interests, Personal, Advisory Board: Eisai, Takeda, Boehringer Ingelheim, Cimic, Chugai, Healios; Financial Interests, Institutional, Local PI, Principal Investigator in industry sponsored trial: Astellas, Chugai, Eisai, Taiho, BMS, Pfizer, Novartis, Eli Lilly, AbbVie, Daiichi Sankyo, Bayer, Boehringer Ingelheim, Kyowa-Hakko Kirin, Takeda, ONO, Janssen Pharma, MSD, Merck, GSK, Sumitomo Dainippon, Chiome Bioscience, Otsuka; Financial Interests, Institutional, Local PI, Principal investigator in industry sponsored trial: Carna Biosciences, Genmab, Shionogi, TORAY; Financial Interests, Institutional, Research Grant, Principal investigator in industry sponsored trial: Rakuten Medical, InventisBio Co., Ltd. J. Raimbourg: Financial Interests, Personal, Speaker, Consultant, Advisor, Honoraria: Sanofi, Pierre Fabre, Takeda, BMS, Amgen, AstraZeneca; Financial Interests, Institutional, Research Funding: Takeda. B.C. Cho: Financial Interests, Personal, Other, Consulting role: Abion, BeiGene, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Medpacto, Blueprint medicines, RandBio, Hanmi, GC Cell, Gilead, Ridgeline Discovery GmbH; Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc., Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc., J INTS Bio, Therapex Co., Ltd., Gilead, Amgen, AstraZeneca, Regeneron, Seagen, Samsung Bioepis; Financial Interests, Personal, Member of Board of Directors: Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Full or part-time Employment: Yonsei University Health System; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc., Gencurix Inc., Bridgebio therapeutics, KANAPH Therapeutic Inc., Cyrus therapeutics, Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Royalties: Champions Oncology, Crown Bioscience, Imagen, PearlRiver Bio GmbH, Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: CHA Bundang Medical Center, MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, Gradiant Bioconvergence, Therapex, GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Onoclogy, CJ bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine, Janssen, Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph therapeutics, JINTSbio, Hanmi, Daewoong Pharmaceutical Co., Ltd., Vertical Bio AG, Korea Institute of Oriental Medicine, National Research Foundation of Korea, KHIDI; Other, Founder: DAAN Biotherapeutics; Other, Invited speaker: ASCO, AstraZeneca, Guardant, Roche, ESMO, IASLC, Korean Cancer Association, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, MSD, The Chinese Thoracic Oncology Society, Pfizer, Liangyihui Network Technology Co., Ltd. J.W. Goldman: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Genentech, Eli Lilly, Janssen, AbbVie, Gritstone; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Eli Lilly; Financial Interests, Institutional, Local PI: Genentech, Janssen, BMS, AbbVie. M.E. Blaney, T. Jennaro, A. Vasilopoulos, R.R. Li, K.J. Freise, M.R. Neagu Aristide, G. Morrison-Thiele, Z.N. Hunter, M. Burns: Financial Interests, Personal, Full or part-time Employment: AbbVie Inc.; Financial Interests, Personal, Stocks/Shares: AbbVie Inc. D.R. Camidge: Financial Interests, Speaker, Consultant, Advisor, Honoraria: AbbVie, Amgen, Astellas BioPharma, Apollomics, AnHeart Therapeutics, AstraZeneca, BeiGene, Bio-Thera Solutions, Blueprint Medicines, 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, Seagen, Takeda, Turning Point Therapeutics; Financial Interests, Institutional, Research Funding: Inivata. All other authors have declared no conflicts of interest.