1646P - A multicohort phase II trial of androgen deprivation therapy (ADT), docetaxel (DOCE) and nivolumab (NIVO) in patients (pts) with newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC) enriched for inflamed tumours and DNA damage repair (DDR) alterations: Cohort 3 results

Background

This is a multicenter, multicohort, phase 2 investigator-initiated trial of ADT, DOCE, and NIVO in pts with de novo mHSPC. Cohort allocation is based on positive tumor PD-L1 and CD8 staining (Cohort 1), presence of DDR alterations (Cohort 2), or absence of biomarkers (Cohort 3). Primary results from Cohort 3 are reported.

Methods

Pts with newly diagnosed mHSPC with ECOG 0-2 and PSA >4.0 ng/mL before ADT initiation were enrolled. Up to 140 days of ADT was allowed pre-enrollment. Pts received continuous ADT, DOCE 75mg/m² and NIVO 360mg Q3W for 6 cycles, followed by NIVO 480mg Q4W for up to 2 years. Primary endpoint: PSA

Results

20 pts were enrolled in Cohort 3 from 5/2020 to 7/2022. Median follow-up was 27.4mo. Median age was 67y (IQR 63-71) and median PSA at ADT initiation was 86 ng/mL (IQR 29-415). 25% (n=5) pts had visceral metastasis, 90% (n=18) had bone metastasis, and 60% (n=12) had nodal metastasis. Volume of metastasis (CHAARTED criteria) was high in 90% (n=18) pts. Rate of PSA

Conclusions

Cohort 3 did not meet the 7mo PSA response primary endpoint. Safety of the combination was consistent with individual profiles of each agent. Results from biomarker positive cohorts, which may enrich for response, will be reported separately.

Clinical trial identification

Clinical trial information: NCT04126070.

Editorial acknowledgement

Legal entity responsible for the study

Xiao X. Wei.

Funding

Bristol Myers Squibb.

Disclosure

X.X. Wei: Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Other, Membership on Biomarker/Immune Response Monitoring Committee (BIRMC): Dendreon; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Institutional, Coordinating PI: Bristol Myers Squibb; Non-Financial Interests, Advisory Role: MacroGenics; Non-Financial Interests, Principal Investigator: Barinthus Biotherapeutics, MacroGenics, Novartis, Poseida. J. Chahoud: Financial Interests, Personal, Advisory Board: Pfizer, Exilisis, Aveo, Eisai, MyCareGorythm. H. Emamekhoo: Financial Interests, Personal, Advisory Board: Janssen, Aveo, Cardinal Health, Eisai, BMS. R.R. McKay: Financial Interests, Personal, Advisory Board: Aveo, AstraZeneca, Bayer, Calithera, Dendreon, Exelixis, JNJ, Merck, Pfizer, Sanofi, Tempus, BMS, Lilly, Sanofi, Seagen, Telix, Sorrento Therapeutics, Eisai, Blue Earth Diagnostics; Financial Interests, Personal, Other, Molecular tumor board: Caris; Financial Interests, Personal, Other, Consultant: Dendreon, Myovant; Financial Interests, Personal, Invited Speaker: Exelixis, Merck, Novartis, Pfizer; Financial Interests, Steering Committee Member: Aveo, Merck, Eli Lilly; Financial Interests, Local PI: JNJ, SeaGen, Calibr, Poseida, Oncternal, Scholar Rock, Merck, Xencor, Genentech, Eli Lilly, BMS; Financial Interests, Trial Chair: Bayer, AstraZeneca; Financial Interests, Institutional, Local PI: Exelixis. C.H. Marshall: Financial Interests, Personal, Invited Speaker: Tempus; Financial Interests, Personal, Royalties: McGraw Hill; Financial Interests, Institutional, Research Grant: AstraZeneca. D. Einstein: Financial Interests, Personal, Advisory Board: Nimbus; Financial Interests, Institutional, Trial Chair: Bristol Myers Squibb, Cardiff Oncology, Puma Biotechnology, MiNK Therapeutics; Financial Interests, Institutional, Research Grant: Novartis, Sanofi. J.M. Lang: Financial Interests, Personal, Advisory Board: Pfizer, Janssen, Gilead, 4D Pharma, Arvinas, Astellas, Myovant, AstraZeneca, Seagen, Macrogenics; Financial Interests, Institutional, Coordinating PI: Gilead; Financial Interests, Institutional, Local PI: Pfizer, Arvinas, Seagen. P. Ravi: Financial Interests, Institutional, Funding: Bayer, Lilly, Telix. A. Tewari: Financial Interests, Personal, Stocks/Shares: B.A.I. Biosciences, Moderna, Inflammatix, Teladoc. S. Rodig: Financial Interests, Institutional, Research Funding: Gilead, Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Immunitas Therapeutics. C. Sweeney: Financial Interests, Personal, Advisory Board, Consultancy: Genentech Roche, Bayer, Astellas, Pfizer, Pfizer, Sanofi, Lilly; Financial Interests, Personal, Other, Consultancy: Janssen, MSD; Financial Interests, Personal, Advisory Board: Point, Cellcentric; Financial Interests, Personal, Advisory Board, Consultant: Advancell; Financial Interests, Personal, Advisory Board, Advisory Boards: BMS; Financial Interests, Personal, Advisory Board, Consutlant: Amphista; Financial Interests, Personal, Stocks/Shares: Leuchemix; Financial Interests, Personal, Stocks/Shares, Consultant: Advancell; Financial Interests, Institutional, Advisory Board, Abiraterone plus cabozantinib: Exelixis; Financial Interests, Institutional, Research Grant: Bayer, Janssen, Astellas, Pfizer, Dendreon, Sanofi. M.E. Taplin: Financial Interests, Personal, Advisory Board, Advisory Board: AstraZeneca, Janssen, Blue Earth, Flare Therapeutics, Pfizer; Financial Interests, Personal, Writing Engagement, Author of UpToDate: UpToDate; Financial Interests, Personal, Invited Speaker, Education: Research to Practice, Physician Education Resource, MJH Healthcare; Non-Financial Interests, Principal Investigator, PI Proteus clinical trial: Johnson & Johnson. All other authors have declared no conflicts of interest.