Abstract 591P
Background
Cluster of differentiation 46 (CD46) is expressed at high level in CRPC and expression is further enriched upon androgen signaling inhibition (ASI) and in treatment-emergent small cell neuroendorcine prostate cancer (t-SCNC). FOR46 is a vc-MMAE antibody-drug conjugate that recognizes a tumor selective epitope of CD46. FOR46 binds to CD46 with high affinity and demonstrates anti-tumor activity in prostate cancer xenografts. A first-in-human study of safety and preliminary efficacy of FOR46 in mCRPC patients (pts) was undertaken.
Methods
Pts with mCRPC, including pts with tSCNC, following progression on at least one prior ASI were enrolled. No prior chemotherapy for mCRPC was allowed. An accelerated titration followed by 3+3 dose escalation design was used. Following excess toxicity (neutropenia and fatigue) in pts with high body mass index (BMO), dosing was changed from actual body weight to adjusted body weight. G-CSF secondary propylaxis was specified for pts experiencing grade (gr) ≥ 3 neutropenia during a previous treatment cycle.
Results
Thrity-three pts were enrolled at 10 dose levels from 0.1 to 3.0 mg/kg. Median age was 66 (range 42-81); median baseline PSA was 41 (range 0.2 - 1627); 7 pts had visceral organ metastases. Dose limiting toxicities were gr 4 neutropenia in 3 of 3 high BMI pts at 2.4 mg/kg dosed by actual body weight and 2 of 3 pts at 3.0 mg/kg dosed by adjusted body weight. The MTD was 2.7 mg/kg by adjusted body weight. The most common related adverse events were gr 4 neutropenia in 11 of 33 pts (33%), gr 3 neutropenia in 6 (18%) and infusion related reactions (IRR) in 14 (42%) with 1 gr 3 IRR. Any gr neuropathy occurred in 7 pts (21%), with 1 gr 3 neuropathy (3%). At 1.2 mg/kg or higher (n = 24), 9 pts (38%) had a PSA50 responnse and 15 (63%) had any decline in PSA. Of 8 pts with measurable disease, 1 partial response was reported and 6 had stable disease lasting from 9 to 39 weeks. The median number of treatment cycles is 6 (range 1-23) with 11 ongoing.
Conclusions
FOR46 demonstrates an acceptable toxicity profile using adjusted body weight dosing, and encouraging preliminary evidence of efficacy in ASI-resistant mCRPC pts. FOR46 is currently being evaluated in 2 mCRPC expansion cohorts: adenocarcinoma and t-SCNC.
Clinical trial identification
NCT03575819.
Editorial acknowledgement
Legal entity responsible for the study
Fortis Therapeutics, Inc.
Funding
Fortis Therapeutics, Inc.
Disclosure
R.R. Aggarwal: Non-Financial Interests, Institutional, Principal Investigator: Fortis Therapeutics. J. Vuky: Non-Financial Interests, Institutional, Principal Investigator: Fortis Therapeutics; Financial Interests, Personal, Advisory Role: Astellas; Non-Financial Interests, Institutional, Principal Investigator: Merck; Financial Interests, Personal, Advisory Role: Seattle Genetics; Non-Financial Interests, Institutional, Principal Investigator: Novartis; Non-Financial Interests, Institutional, Principal Investigator: Roche/Genentech; Non-Financial Interests, Institutional, Principal Investigator: Innocrin Pharma; Non-Financial Interests, Institutional, Principal Investigator: Celldex; Non-Financial Interests, Institutional, Principal Investigator: Arvinas. D. VanderWeele: Financial Interests, Personal, Advisory Role: Clovis Oncology; Financial Interests, Personal, Advisory Role: Genentech; Financial Interests, Institutional, Research Grant: AstraZeneca; Non-Financial Interests, Institutional, Principal Investigator: Fortis Therapeutics, Inc. M. Rettig: Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Ambrx; Financial Interests, Personal, Advisory Role: Roivant; Financial Interests, Institutional, Research Grant: Johnson & Johnson; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Johnson & Johnson; Non-Financial Interests, Institutional, Principal Investigator: Fortis Therapeutics, Inc. E. Heath: Non-Financial Interests, Institutional, Principal Investigator: Fortis Therapeutics; Other, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Bayer; Other, Personal, Other: Caris Life Science; Financial Interests, Personal, Speaker’s Bureau: Sanofi; Financial Interests, Personal, Advisory Board: Seattle Genetics. M. Nasoff: Financial Interests, Personal, Officer: Fortis Therapeutics. A. Dorr: Financial Interests, Personal, Officer: Fortis Therapeutics; Financial Interests, Personal, Officer: BrightPath BioTherapeutics; Financial Interests, Personal, Officer: Curegenix; Financial Interests, Personal, Officer: Cend Therapeutics; Financial Interests, Personal, Officer: Phoenix Molecular Designs; Financial Interests, Personal, Advisory Role: Virtuoso BINCO; Financial Interests, Personal, Officer: Vivace Therapeutics. B. Liu: Financial Interests, Personal, Member of the Board of Directors: Fortis Therapeutics, Inc; Financial Interests, Personal, Stocks/Shares: Vivace Therapeutics; Financial Interests, Personal, Advisory Role: Merck Sharpe and Dohme. E.J. Small: Financial Interests, Personal, Advisory Role: Fortis Therapeutics.