163P - Genomic alterations in circulating tumor DNA (ctDNA) and response to ABBV-400 treatment in patients with advanced solid tumors

Background

Several solid tumors, including colorectal cancer (CRC), overexpress c-Met. The antibody-drug conjugate ABBV-400 comprises the c-Met–targeting antibody telisotuzumab conjugated to a potent topoisomerase 1 inhibitor payload. ABBV-400 is being evaluated in a phase 1 trial (NCT05029882) in patients (pts) with advanced solid tumors. We analyzed correlations between genomic alterations and response of pts in this study.

Methods

Adults with advanced solid tumors and no validated treatment option were enrolled. Intravenous ABBV-400 was administered once every 3 weeks. ctDNA was isolated from plasma and analyzed using the GuardantINFINITY™ assay that evaluated various parameters including single-nucleotide variants and insertion-deletion mutations (753 genes), amplifications (415 genes), tumor mutational burden (TMB), and microsatellite instability (MSI) status. Molecular response (based on ctDNA variant allele frequencies) and radiographic response (RECIST v1.1) were assessed.

Results

As of 3 April 2023, 57 pts were efficacy evaluable, including 27 pts with CRC. The objective response rate was 25% (14/57; all confirmed partial responses [cPR]) in all pts and 22% in pts with CRC (6/27; all cPR). Most prevalent gene alterations were TP53 (67%), LRP1B (43%), APC (41%), and KRAS (41%) mutations and PTPRT (45%) and TOP1 (43%) amplifications. The table shows the correlation between response and select biomarkers (at baseline) in the 45 pts (22 CRC) who had both ctDNA and radiographic response data. A molecular response was observed in 48% (14/29) of all evaluated pts and 47% (8/17) of pts with CRC; median change from baseline tumor size was -22.5% and -20.3%, respectively. Table: 163P

Pts with molecular response and correlation between baseline biomarker status and radiographic response

^a29 pts were evaluable for molecular response. ^b17 CRC pts were evaluable for molecular response. CRC, colorectal cancer; MSI, microsatellite instability; mut, mutations; PR, partial response; pts, patients; TMB, tumor mutational burden.

Conclusions

ABBV-400 showed promising preliminary efficacy, with molecular and radiographic responses in pts with advanced solid tumors with heterogeneous genomic profiles, including in pts with high TMB and KRAS mutations.

Clinical trial identification

NCT05029882.

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 funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the abstract. All authors had access to relevant data and participated in the drafting, review, and approval of this abstract. No honoraria or payments were made for authorship.

Funding

AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the abstract. All authors had access to relevant data and participated in the drafting, review, and approval of this abstract. No honoraria or payments were made for authorship.

Disclosure

J. Bar: Financial Interests, Personal, Advisory Role: AbbVie, AstraZeneca, Bayer, BMS, Causalis, Eisai, MSD, Novartis, Roche, Takeda; Financial Interests, Personal, Research Funding: ImmuneAI, OncoHost, MSD, AstraZeneca. M.R. Sharma: Financial Interests, Personal, Advisory Role: Pliant Therapeutics; Financial Interests, Personal, Stocks or ownership: AbbVie, Biogen, Bristol Myers Squibb, Lilly, Merck, Pfizer, Regeneron, Amgen, Gilead Sciences, Johnson & Johnson, Janssen, Moderna Therapeutics, Vertex, West Pharmaceutical; Financial Interests, Personal, Research Funding: Ascentage Pharma, AstraZeneca, Bolt Biotherapeutics, BMS, Compugen, Constellation Pharmaceuticals, CytomX Therapeutics, Exelixis, Ikena Oncology, Inhibrx, Jounce Therapeutics, KLUS Pharma, Loxo, MacroGenics, Merck, Pfizer, Regeneron, Symphogen, Syros Pharmaceuticals, Astellas Pharma, Celgene, Treadwell Therapeutics, PureTech, GSK/Tesaro, Seattle Genetics, Shattuck Labs, Sapience Therapeutics, Epizyme, Odonate Therapeutics, Tempest Therapeutics, Mersana, NGM Biopharmaceuticals, Samumed, Onconova Therapeutics, Gilead Sciences, AbbVie, Agenus, Alkermes, Alpine Immune Sciences, Alexo Therapeutics, Johnson & Johnson/Janssen, Seven and Eight Biopharmaceuticals, Cullinan Oncology, Debiopharm Group, Palleon Pharmaceuticals, Helsinn Therapeutics, Kinnate Biopharma, KSQ Therapeutics, Repare Therapeutics, SK Life Sciences, Theratechnologies, Tizona Therapeutics Inc. Y. Kuboki: Financial Interests, Personal, Research Funding: Taiho, Astellas, Lilly, Takeda, Daiichi Sankyo, AstraZeneca, Boehringer Ingelheim, Chugai, Genmab, GSK, Incyte, AbbVie, Amgen; Financial Interests, Personal, Advisory Role: Takeda, Amgen, Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria: Taiho, Lilly, Bristol Myers Squibb. R. Perets: Financial Interests, Personal, Advisory Role: Galmed Pharmaceuticals, Gilboa Therapeutics, 1E Therapeutics; Financial Interests, Personal, Other, Honoraria: MSD. D. Sommerhalder: Financial Interests, Personal, Other, Employee: Texas Oncology, US Oncology; Financial Interests, Personal, Other, Honoraria: Syneos; Financial Interests, Personal, Research Funding: AbbVie, ADC Therapeutics, Ascentage Pharma Group, Astellas, Biomea Fusion, Boehringer Ingelheim, BJ Bioscience, BioNTech, Fate Therapeutics, Gilead Sciences, Immuneering, Kura Oncology, Monopteros Therapeutics, Navire Pharma Inc, Nimbus Saturn Inc, NGM Biopharmaceuticals, Parthenon, Pfizer, Revolution Medicines, Mirati Therapeutics, Symphogen, Teon Therapeutics, Medilink Therapeutics, ZielBio Inc. N. Yamamoto: Financial Interests, Personal, Research Grant: Astellas, Chugai, Eisai, Taiho, BMS, Pfizer, Novartis, Eli Lilly, AbbVie, Daiichi Sankyo, Bayer, Boehringer Ingelheim, Rakuten Medical, Kyowa Kirin, Takeda, Ono, Janssen Pharma, Merck Sharp & Dohme, Merck, GSK, Sumitomo Pharma, Chiome Bioscience, Otsuka, Carna Biosciences, Genmab, Shionogi, Toray, Kaken, AstraZeneca, Cimic, InventisBio, Rakuten Medical; Financial Interests, Personal, Other, Personal fees: Ono Pharmaceutical, Chugai, Daiichi Sankyo, Eisai, Takeda, Otsuka, Boehringer Ingelheim, Cimic, Healios. J. Powderly: Financial Interests, Personal, Other, Consulting: Boxer Capital; Financial Interests, Personal, Writing Engagement, Consulting: Aavocyte; Financial Interests, Personal, Member of Board of Directors, Founder and Owner: Carolina BioOncology Institute, PLLC, BioCytics Inc.; Financial Interests, Personal, Ownership Interest, Founder and Owner: BioCytics Inc.; Financial Interests, Personal, Ownership Interest, Founder and Owner of phase 1 cancer research clinic: Carolina BioOncology Institute, PLLC; Financial Interests, Personal, Other, Founder and Owner, developing intellectual property for cellular therapies: BioCytics Inc; Financial Interests, Personal and Institutional, Local PI: Bristol Myers Squibb, Cullinan, Genentech/Roche, AstraZeneca/MedImmune, EMD Serono, Macrogenics, InCyte, Top Alliance BioSciience, Seattle Genetics, AbbVie, FLX Bio, Alkermes, Arcus BioSciences, Tempest Therapeutics, Calico Life Sciences, Apros, Jounce Therapeutics, Atreca, Sequenom, Repertoire Immune Medicines, Molecular Templates, I-MAB Pharma, NexCure, Xilio Therapeutics, Immune-Onc, Trethera, Zenshine Pharma, Adagene, BJ BioScience, Fate Therapeutics, Conjupro BioTherapeutics, PEEL Therapeutics, CUE BioPharma, Pieris Pharmaceuticals, RiboScience, Moderna TX, Phanes Therapeutics, SK Life Science, Harbour BioMed, Simcere, Allarity, Aulos, GI Innovation, IGM BioSciences, Aptevo, Medikine, IconOVir Bio, Qurgen; Financial Interests, Institutional, Funding: Precision for Medicine, MT Group, STEMCELL Technologies, Replimmune, Merck, Xilis; Financial Interests, Personal and Institutional, Funding: PIOMA; Financial Interests, Personal and Institutional, Local PI, Also funding for contract laboratory services: Nuvation; Financial Interests, Personal and Institutional, Funding, Wugen is sponsor of contract laboratory translational research: Wugen; Financial Interests, Personal and Institutional, Other, AavoCyte & AavoBioCytics are jointly developing cellular therapies with BioCytics Human Applications Lab for point of care manufacturing: AavoCyte; Other, As Founder and Owner of BioCytics Inc. developing immune cellular therapy: BioCytics Inc. J.H. Strickler: Financial Interests, Personal, Other, Consulting: AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Daiichi Sankyo, Eli Lilly, GSK, Natera, Pfizer, Pionyr Immunotherapeutics, Roche/Genentech, Seagen, Silverback Therapeutics, Takeda, Viatris, Zentalis; Financial Interests, Personal, Research Funding: AbbVie, Amgen, AStar D3, Bayer, BeiGene, Curegenix, Daiichi Sankyo, Eli Lilly, Erasca, Gossamer Bio, Leap Therapeutics, Nektar, Roche/ Genentech, Seagen, Silverback Therapeutics. M. Li, A. Luo, G. Morrison-Thiele, M.R. Neagu Aristide, A. Vasilopoulos: Financial Interests, Personal, Stocks/Shares, Employee and may own stock: AbbVie Inc. D.R. Camidge: Financial Interests, Personal, Other, 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, Personal, Research Funding: Inivata (Inst).