Abstract 1406P
Background
Resistance to ARSIs (e.g. abiraterone, enzalutamide) is inevitable and there is critical need to develop new therapies for mCRPC. SG is an antibody-drug conjugate targeting Trop-2, currently FDA-approved for use in breast and bladder cancers.
Methods
An open label, phase II trial of SG for pts with mCRPC progressing on ARSIs, stratified by prior chemo vs. chemo naïve, was opened to evaluate the efficacy of SG. Pts were required to have rising PSA and radiographic progression on ARSI in the mCRPC setting. The two primary endpoints were 6-month radiographic progression-free survival (rPFS) and PSA50 response. A separate analysis of Trop-2 expression in prostate cancer biopsies and association with genomic markers of ARSI resistance were also analyzed in 4 previously curated cohorts (n = 632) and the PROMOTE study (n = 88).
Results
Twenty pts were enrolled in this Phase II trial at the time of interim analysis. Pts had a median PSA of 47.2ng/mL at baseline. All pts had metastatic disease, with 90% bone only metastases. All pts had progressed on an ARSI with 30% of pts having received docetaxel chemotherapy in the castration sensitive setting. Neutropenia was the most common adverse event (AE) across all grades, observed in 85% of pts though easily managed with GCSF and only 1 episode of febrile neutropenia. Nausea, diarrhea, anemia, and alopecia were observed in ≥50% of pts, with only four grade 3 AEs. The 6-month rPFS rate was 45% in all pts and 64% of chemo-naïve pts, with the longest treated pt on trial for 62 weeks. No PSA50 responses were observed although PSA stabilization occurred in all pts that met the 6-month rPFS endpoint. We also report that Trop-2 is expressed in >80% of pts with mCRPC and associated with luminal and basal subtypes, suggesting Trop-2 as a high value therapeutic target in mCRPC.
Conclusions
SG has clinical activity in mCRPC progressing on prior ARSI(s) based on 6-month rPFS, which warrants further clinical investigation. PSA stabilization was observed in pts meeting this endpoint. Analysis of tissue and liquid biopsies is ongoing to identify predictive biomarkers for SG in prostate cancer.
Clinical trial identification
NCT03725761.
Editorial acknowledgement
Legal entity responsible for the study
Carbone Cancer Center, University of Wisconsin-Madison.
Funding
Gilead, Prostate Cancer Foundation.
Disclosure
J. Lang: Financial Interests, Personal, Advisory Board: Pfizer, Janssen, Gilead, 4D Pharma, Arvinas, Astellas, Myovant, AstraZeneca, Seagen; Financial Interests, Institutional, Invited Speaker: Gilead, Pfizer, Arvinas, Seagen. S.T. Tagawa: Financial Interests, Personal, Advisory Board: Convergent Therapeutics, AIkido Pharma; Financial Interests, Personal, Other, Consultant: EMD Serono, Telix Pharma, Blue Earth Diagnostics, POINT Biopharma, Myovant, Bayer, 4D Pharma, Gilead, Pfizer, Janssen, Astellas, AbbVie, Novartis, Seagen, Clarity; Financial Interests, Personal, Stocks/Shares: AIkido Pharma; Financial Interests, Personal, Other, Patent co-inventor: Gilead; Financial Interests, Institutional, Invited Speaker: Medivation, Astellas, Janssen, Amgen, BMS, AstraZeneca, Bayer, Merck, Clovis, Seagen, Gilead, Novartis, POINT Biopharma, Clarity, Ambrx, Phosplatin. S. Slovin: Financial Interests, Personal, Invited Speaker, Speaker: Physician Education Resource; Financial Interests, Personal, Other, Grant Reviewer: NCI; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Clovis, LabCorp. H. Emamekhoo: Financial Interests, Personal, Advisory Board: Exelixis, Seattle Genetics. D. Rathkopf: Financial Interests, Invited Speaker: Janssen, Janssen, Genentech; Financial Interests, Research Grant: Genentech; Non-Financial Interests, Advisory Role: Janssen, Genentech, AstraZeneca, Myovant; Non-Financial Interests, Principal Investigator: Janssen, Genentech, Phosplatin, Taiho, Celgene/BMS; Non-Financial Interests, Other, Drug supplied by Bayer for Investigator-led trial: Bayer. W. Abida: Financial Interests, Personal, Invited Speaker: Roche, Medscape, Aptitude Health, Onclive, Clinical Education Alliance, TouchIME; Financial Interests, Personal, Advisory Board: Clovis Oncology, Janssen, ORIC Pharmaceuticals, Daiichi, AstraZeneca UK; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Zenith Epigenetics, Clovis Oncology, ORIC Pharmaceuticals, Epizyme; Non-Financial Interests, Member: ASCO. K. Autio: Financial Interests, Institutional, Invited Speaker, Funding to institution for trial conduct: Amgen, Lilly, Parker Institute for Cancer Immunotherapy, AstraZeneca, Trishula, GSK; Financial Interests, Institutional, Invited Speaker, Lead PI - Funding to institution for trial conduct: Pfizer. A.M. Molina: Financial Interests, Personal, Advisory Board: Janssen, Eisa, Exelixis. J. Eickhoff: Financial Interests, Personal, Other, Consultant: AbbVie. S. Dehm: Financial Interests, Personal, Other, Scientific Consultant: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Oncternal Therapeutics. D.M. Nanus: Financial Interests, Personal, Invited Speaker, Participated in roundtable: AstraZeneca; Financial Interests, Institutional, Invited Speaker, PI Clinical Trial: Exelixis; Financial Interests, Institutional, Invited Speaker, Site Lead Clinical Trial: Zenith Epigenetics. C.E. Kyriakopoulos: Financial Interests, Personal, Advisory Board: Exelixis, AVEO, Sanofi-Aventis, EMD Serono, Janssen Pharmaceuticals; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Gilead, Incyte Corporation, Sanofi-Aventis, AstraZeneca. All other authors have declared no conflicts of interest.