1660TiP - First-in-human study of ABBV-969, a dual variable antibody-drug conjugate (ADC), in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)

Background

A high unmet therapeutic need exists in mCRPC, which remains incurable. Expression of six-transmembrane epithelial antigen of prostate 1 (STEAP1) is highly enriched in >85% of PC, and in pts with mCRPC, prostate-specific membrane antigen (PSMA) expression is >100-fold higher. Both are well characterized PC antigens and actionable targets in mCRPC. ABBV-969 is a dual variable domain IgG1 drug conjugate comprising PSMA and STEAP1 binding domains and a topoisomerase 1 inhibitor (Top1i) payload. Based on preclinical and clinical data of other Top1i ADCs, ABBV-969 is expected to have improved efficacy and broader breadth of activity vs targeting either antigen alone. We describe a first-in-human study of ABBV-969 in pts with mCRPC.

Trial design

This phase 1 open-label study (NCT06318273) evaluates safety, pharmacokinetics (PK), and efficacy of ABBV-969 monotherapy. Eligible pts (≥18 yr) have mCRPC treated with and progressed on ≥1 prior novel hormonal agent for mCRPC/CRPC and ≥1 taxane for PC (or have refused/intolerant/unable to access taxanes). Pts must have serum PSA levels ≥1.0 ng/mL, serum testosterone levels ≤50 ng/dL, ≥1 metastatic lesion at baseline, life expectancy >6 months. Part 1 (dose escalation) is guided by the Bayesian optimal interval design primarily based on the rate of DLT occurrence. Up to ∼60 pts will be enrolled; DLTs are assessed during the first dosing cycle. Part 2 (dose expansion) will randomize ∼60 pts in 2 (1:1) or 3 (1:1:1) dose levels (determined in part 1). Optimal dose (recommended phase 2 dose) will be determined by the totality of PK, pharmacodynamic, safety, and efficacy data. Pts will receive ABBV-969 IV until disease progression, intolerable toxicity, or other study discontinuation criteria are met. Objectives and endpoints are shown in the table. Pts will be enrolled in US, Israel, Japan, and Australia in part 1; additional locations may be added. Table: 1660TiP

Clinical trial identification

NCT06318273.

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

A.W. Tolcher: Financial Interests, Personal, Ownership Interest: NEXT Oncology. T.B. Dorff: Financial Interests, Personal, Advisory Board: AstraZeneca, Janssen, Sanofi, Bayer. S. Okubo, L.S. Abraham, R. Reilly, C. Stevenson, S. Wang, J. Arnold, S.R. Mudd, S. Alaei, J. Hong, D.I. Quinn: Financial Interests, Personal, Full or part-time Employment: AbbVie Inc.; Financial Interests, Personal, Stocks/Shares: AbbVie Inc. F. Saad: Financial Interests, Personal, Advisory Board: Astellas, Bayer, BMS, Janssen, Pfizer, Myovant, Novartis, AstraZeneca, Merck; Financial Interests, Institutional, Local PI: Novartis, Astellas, Bayer, Janssen, Sanofi, BMS, Amgen, Pfizer, Merck; Financial Interests, Institutional, Coordinating PI: AstraZeneca. 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. All other authors have declared no conflicts of interest.