1652P - SAABR: Single arm phase II study of androgen receptor pathway inhibitor (ARPI) + atezolizumab + GnRH analog (ADT) and stereotactic body radiotherapy (SBRT) to the prostate in men with de novo hormone-sensitive metastatic prostate cancer (mHSPC)

Background

Metastatic hormone-sensitive prostate cancer (mHSPC) is generally thought to be immunologically cold. Emerging data suggest that radiotherapy and androgen ablation may augment anti-tumor immune response to anti-PD-L1 therapy and improve outcomes compared to standard-of-care. We sought to test this hypothesis in participants (pts)with de novo mHSPC, a population with a poor prognosis.

Methods

SAABR was designed to enroll 42 pts. All pts were first started on atezolizumab followed by initiation of ARPI and ADT at month 1 and SBRT to the prostate at month 5. Intra-prostatic fiducial markers and biopsy were done in the first 20 pts (Cohort 1) while on atezolizumab alone. The remaining pts (Cohort 2) were on tri-modal therapy (atezolizumab, ADT, and ARPI) at the time of fiducials and biopsy. The primary, composite endpoint was freedom from failure (biochemical recurrence, radiographic progression, early withdrawal, and death) at 2 years. After 3 serious adverse events (AEs) the trial was closed to accrual; 28 pts were enrolled.

Results

After 3 treatment-related serious AEs (Grade 4 colonic perforation in 2 pts and Grade 5 hemophagocytic lymphocytosis in 1 pt) the trial was closed to accrual. Twenty-eight pts (Cohort 1 n=20, Cohort 2 n=8) were enrolled and treated with at least one dose of atezolizumab. Median age was 65 years (range 58-70), 82% had bone metastasis, 18% had M1a lymph node-only disease, 26% had HRR mutations, and the median PSA at diagnosis was 20.46 ng/dL (range 2.8-1276.33). 64% of pts were failure-free at 2 years; 17% had biochemical failure, 11% had radiographic progression, and 7% were off-study prior to 2 years. Treatment-related AEs occurred in 93% of pts. Grade 3-5 treatment-emergent AEs occurred in 39% of pts. There was 1 Grade 5 AE of hemophagocytic lymphocytosis.

Conclusions

Maximal hormonal blockade (ADT + ARSI) combined with atezolizumab plus SBRT to the prostate is associated with significant toxicity and only modest activity in mHSPC.

Clinical trial identification

NCT04262154.

Editorial acknowledgement

Legal entity responsible for the study

Dana Rathkopf.

Funding

Genentech; Stand up to Cancer.

Disclosure

D. Rathkopf: Financial Interests, Trial Chair: Janssen; Financial Interests, Steering Committee Member: Janssen; Financial Interests, Institutional, Research Grant, Clinical Trial Grant: Genentech; Non-Financial Interests, Advisory Role: Janssen, Genentech, AstraZeneca, Myovant, Bayer, BMS; Non-Financial Interests, Principal Investigator: Janssen, Genentech, Promontory, BMS, BMS. M. Dallos: Financial Interests, Personal, Advisory Board: BMS, Sanofi. M. Stein: Financial Interests, Personal, Advisory Board: Merck Sharp and Dohme, Exelixis, Xencor, Janssen Oncology, Vaccitech, Bristol Myers Squibb/Medarex; Financial Interests, Institutional, Local PI: Janssen Oncology, Seattle Genetics, Regeneron, Bicycle Therapeutics, OncoC4; Financial Interests, Institutional, Research Grant: Advaxis; Financial Interests, Institutional, Trial Chair: Bristol Myers Squibb, Exelixis; Financial Interests, Institutional, Coordinating PI: Xencor. C.S. Spina: Financial Interests, Personal, Advisory Board, SAB for Radiotherapy trials: Johnson and Johnson; Financial Interests, Personal, Other, Consultant: Johnson and Johnson; Financial Interests, Institutional, Research Grant: Johnson and Johnson; Financial Interests, Institutional, Funding, Provide drug for preclinical studies: Arcus Biosceinces; Financial Interests, Institutional, Other, Sponsor of IIT: Arcus Biosciences. S. McBride: Financial Interests, Personal, Advisory Board: Pfizer, Janssen, Bayer. All other authors have declared no conflicts of interest.