Abstract 1606P
Background
Immune checkpoint inhibition (ICI) rarely with efficacy in mCRPC. EBRT may help; PSMA targeted radionucleotides deliver radiation to multiple sites, alpha emitters cause double-stranded DNA breaks which may be immunogenic. ARI may increase PSMA and PD-L1 + radiosensitze. We hypothesize that alpha-PSMA (225Ac-J591) leads to release of neoantigens and improves response to ICI.
Methods
Eligibility: Progressive mCRPC by PCWG3 criteria (at least one prior ARPI, no chemotherapy in the mCRPC setting). Treatment: ARI of physician’s choice (enza/apa/darolutamide), pembro (pembro 400mg every 6 weeks), and single infusion of 225Ac-J591 at two different dose levels (65 or 80 KBq/kg). Primary endpoint; determination of recommended phase 2 dose (RP2D). Clinical parameters including PSA decline, PFS, OS, and PSMA-PET/CT were analyzed.
Results
Two cohorts: 6 at 65 KBq/kg, 6 at 80 KBq/kg, all with at least 1 prior ARPI (58% prior abi, 58% enza, 8% apa; 17% abi + ARI), 42% sip-T, 17% 177Lu-PSMA. Median age 66.5, median PSA 7.75 ng/mL, 2 (17%) CALGB poor risk, 6 (50%) intermediate; 11 (92%) with bone metastases. With pembro, 7 (58%) received enza 3 (25%) apa, and 2 (17%) daro. No pt with MSI or high TMB (3 with germline BRCA2/CHEK2). No dose-limiting toxicity occurred and the RP2D was determined to be 80 KBq/Kg. A possibly delayed cytokine release syndrome of transient fever, thrombocytopenia, rash, and/or transaminitis occurred approx. 10 days after treatment in 58%. All patients had PSA decline, with 33% treated with 65 KBq/kg having >50% PSA decline and 67% in the 80 KBq/Kg group. All pts in the 65 KBq/kg group had progression (median PFS 5.4 months), whereas 50% in the 80 KBq/kg group completed 2 years of pembro and remain without progression. Median overall survival was 24 months in the 65 KBq/kg group, while 5 patients (83%) in the 80 KBq/kg group remain alive. Baseline median SUVmax whole body was 48.7 (55.5 in 66 KBq, 31.5 in 80 KBq) and the median SUVmean was 8.6 (similar in both groups).
Conclusions
The addition of 225Ac-J591 to pembro and ARI appears promising, with half of patients at 80 KBq/kg having durable response. The randomized phase II trial of pembro/ARI +/- 225Ac-J591 is ongoing (NCT04946370).
Clinical trial identification
NCT04946370.
Editorial acknowledgement
Legal entity responsible for the study
Scott T. Tagawa, Weill Cornell Medicine.
Funding
Weill Cornell Medicine, US Department of Defense, Merck.
Disclosure
D.M. Nanus: Financial Interests, Personal, Advisory Board: tELIX; Financial Interests, Personal, Invited Speaker: Janssen Oncology; Financial Interests, Personal, Other, DSMB Member: Genentech Roche; Financial Interests, Institutional, Coordinating PI, PI clinical trial: Exelixis; Financial Interests, Institutional, Local PI, Site lead clinical trial: Zenith Epigenetics. N.H. Bander: Financial Interests, Personal, Leadership Role: Convergent Therapeutics; Financial Interests, Personal, Licencing Fees or royalty for IP: Telix. S.T. Tagawa: Financial Interests, Personal, Advisory Board: Convergent Therapeutics, AIkido Pharma; Financial Interests, Personal, Other, Consultant: Ambrx, Telix Pharma, Blue Earth Diagnostics, POINT Biopharma, Myovant, Bayer, 4D Pharma, Gilead, Pfizer, Janssen, Astellas, AbbVie, Novartis, Seagen, Clarity, Merck, EMD Serono, Regeneron, Daiichi Sankyo; Financial Interests, Personal, Other, DSMB: Boston Scientific; Financial Interests, Personal, Stocks/Shares: AIkido Pharma; Financial Interests, Personal, Other, Patent co-inventor: Gilead; Financial Interests, Institutional, Advisory Board, Patent: Convergent Therapeutics; Financial Interests, Personal, Advisory Board, Patent: Convergent Therapeutics; Financial Interests, Institutional, Local PI: Medivation, Astellas, Janssen, Amgen, BMS, AstraZeneca, Bayer, Merck, Clovis, Seagen; Financial Interests, Institutional, Steering Committee Member: Gilead, Novartis, POINT Biopharma, Clarity, Ambrx, Promontory, Telix. All other authors have declared no conflicts of interest.
Resources from the same session
1607P - Association of the lipid biomarker, PCPro, and clinical outcomes in the ENZAMET trial (ANZUP 1304)
Presenter: Lisa Horvath
Session: Poster session 10
1608P - Prostate cancer working group 4 (PCWG4) preliminary criteria using serial PSMA PET/CT for response evaluation: Analysis from the PRINCE trial
Presenter: Michael Hofman
Session: Poster session 10
1609P - PSMA-PET and PROMISE re-define stage and risk in patients with prostate cancer
Presenter: Wolfgang Fendler
Session: Poster session 10
1610P - Circulating tumour cell (CTC) enumeration and overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC) treated with xaluritamig
Presenter: Andrew Armstrong
Session: Poster session 10
1611P - Haematologic impact of [177Lu]Lu-PSMA-617 versus ARPI change in patients with metastatic castration-resistant prostate cancer in PSMAfore
Presenter: Kim Nguyen Chi
Session: Poster session 10
1612P - Impact of FANCA, ATM, CDK12 alterations on survival in metastatic castration-resistant prostate cancer (mCRPC)
Presenter: David Lorente
Session: Poster session 10
1613P - Clinically advanced prostate cancer (CAPC) featuring BRCA2 loss: A comprehensive genomic profiling (CGP) study
Presenter: Chiara Mercinelli
Session: Poster session 10
1614P - PSA responses and PSMA scan changes after immunotherapy for biochemically recurrent prostate cancer (BCR) without androgen deprivation therapy (ADT)
Presenter: Ravi Madan
Session: Poster session 10
1615P - A new prognostic model of overall survival (OS) in patients (pts) with metastatic hormone sensitive prostate cancer (mHSPC)
Presenter: Susan Halabi
Session: Poster session 10