The PRIME-CUT study: A single-arm phase 2 study of ADT with PD-1 blockade and docetaxel in men with metastatic hormone-sensitive prostate cancer.
Authors: Hawley Jessica E. , Dallos Matthew , Lim Emerson A. , Runcie Karie , Hu Jianhua , Lowy Israel , Drake Charles G. , Stein Mark N. 
Published: June 2023

e17089 Background: Overall survival of patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC) is improved with androgen deprivation therapy (ADT) and treatment intensification. Initially, ADT induces a robust and functional immune infiltrate into the tumor microenvironment (TME), with upregulation of immune checkpoint molecules. These effects diminish as castration-resistant prostate cancer (CRPC) invariably develops. We report the first results of the phase 2 PRIME-CUT study (modulating the PRostate cancer Immune MicroEnvironment with ChemoimmUnoTherapy for metastatic prostate cancer). Methods: Eligible pts had newly diagnosed mHSPC, ECOG performance status (PS) 0 or 1, serum testosterone levels > 150 ng/dL, agreed to undergo serial metastatic tumor biopsies, and had not received ADT in the prior 6 months. Treatment consisted of ADT (degarelix 240 mg subcutaneously (SC) for one dose, followed by leuprolide 22.5 mg SC every 12 weeks) followed by anti-PD-1 antibody (cemiplimab 350 mg IV every 3 weeks) beginning four weeks after ADT initiation. With the intent of immune priming, a two-cycle lead-in of anti-PD-1 therapy was administered prior to standard of care docetaxel (75 mg/m2 every 3 weeks for six cycles). Participants received ADT and cemiplimab until study completion (52 weeks) or until a lack of clinical benefit or intolerable side effects. The primary endpoint was the rate of undetectable PSA at 6 months after chemotherapy initiation (week 37) and compared to the historical rate from the phase III CHAARTED trial (32%). Subjects were monitored for toxicity using a Bayesian adaptive study design with an early stopping rule for toxicity. Results: The study completed accrual of 20 pts (median age 62 years) from Columbia University Irving Medical Center in Aug 17, 2022. Among them, 7 self-identified race as Black and 12 self-identified their ethnicity as Hispanic. Baseline PSA ranged from 8.15 to > 5000 ng/dL (median 2513.1 ng/dL). Site of metastatic disease included: 17/20 bone, 12/20 lymph nodes, 11/20 visceral organs. Overall, 14 of 20 patients received at least 4 cycles of docetaxel. Of the 12 patients that were still on-study at 37 weeks, 2 had an undetectable PSA, and 4 additional pts had PSA < 1.0 ng/dL. Twelve pts experienced ≥ Grade 3 adverse events (AEs), 6 AEs were attributed to study intervention including cytopenias (3), hypotension (1), pneumonitis (1), and stenosis of gastrointestinal stoma (1). Unfortunately, two patients deceased on-study (myocardial infarction after 13 weeks, severe SARS-CoV-2 infection after 19 weeks). Conclusions: The Prime-Cut study did not meet its primary endpoint. However, PSA kinetics and results from the pre-planned correlative science demonstrate ongoing role for immunotherapeutic approaches in mHSPC. No new safety signals were observed. Clinical trial information: NCT03951831 .