Abstract 1388P
Background
Immune checkpoint blockade (ICB) is approved for mCRPC pts with a tumor mutational burden (TMB) of > 10 mutations per megabase (mut/Mb) or mismatch repair deficiency (dMMR). More pts may benefit, particular those with DNA damage repair alterations and moderately elevated TMB. In mCRPC, nivo/ipi is more effective than monotherapy, but the applicability of nivo1/ipi3 is limited by its toxicity. This study investigates the efficacy and safety of nivo3/ipi1 in molecular-selected pts. Here, we present the results of a preplanned interim safety analysis.
Methods
In this single arm, phase II trial, 75 molecular-selected mCRPC pts will be included, all ECOG performance status 0-1. Molecular selection criteria comprise dMMR, non-synonymous TMB >7 mut/Mb, BRCA2 and CDK12 inactivation. The main study cohort (A1, n=50) consists of ICB-naïve pts with RECIST1.1 measurable disease. Safety is evaluated in cohorts A1, A2 (non-measurable disease) and B (prior ICB monotherapy). Pts are treated with nivo3/ipi1 Q3W for 4 cycles, followed by nivo 480 mg Q4W up to 1 year. Primary endpoint is disease control rate at 6 months. This interim analysis was performed in 25 pts with ≥ 17 weeks of follow up and aimed at < 35% toxicity-related discontinuations before week 17.
Results
The first 25 pts initiated treatment (Tx) between January and November 2021. Median number of prior CRPC Txs was 1 [range 0-5]. At data cut off, the median duration of study Tx was 128 days [range 21-371]. Tx-related AEs (TRAEs) led to discontinuation in 5 pts (20%). Four pts (16%) discontinued before week 17. Median number of combination doses was 3 [range 1-4]. Thirteen pts (52%) did not receive all 4 combination doses due to TRAEs (n=6, 24%) or disease progression (n=7, 28%). TRAEs of any grade occurred in 24 pts (96%; grade 3–4: 10, 40%). The most common grade 3–4 TRAEs were increases in ALAT, ASAT and GGT (n=3 for each, 12%) and decreases in lymphocyte count (n=4, 16%). There were no Tx-related deaths. PSA declines ≥50% were seen in 13 pts (52%) across molecular subgroups. Four pts (25%) showed an objective response.
Conclusions
Nivo3/ipi1 showed an acceptable safety profile in this interim analyses in mCRPC pts.
Clinical trial identification
NCT04717154, EudraCT 2020-001240-25.
Editorial acknowledgement
Legal entity responsible for the study
Radboud University Medical Center.
Funding
Bristol Myers Squibb Company.
Disclosure
M. den Brok: Financial Interests, Personal, Full or part-time Employment: Tagworks Pharmaceuticals, ERC immunotherapeutics. J. Schalken: Non-Financial Interests, Personal, Advisory Role: MDxHealth; Financial Interests, Personal, Other: Bayer. W.R. Gerritsen: Financial Interests, Institutional, Advisory Board: MSD, IMS Health, BMS; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal and Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Research Grant: Bayer, Astellas; Non-Financial Interests, Principal Investigator: MSD, BMS. N. Mehra: Financial Interests, Personal, Advisory Board: Pfizer, Roche, MSD, AstraZeneca, Astellas, JNJ; Financial Interests, Institutional, Advisory Board: Janssen; Financial Interests, Institutional, Funding: Astellas, Pfizer; Financial Interests, Personal and Institutional, Funding: Janssen; Financial Interests, Institutional, Invited Speaker: BMS, Janssen, BMS; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS; Non-Financial Interests, Leadership Role, Head of the Prostate Cancer Working group: Dutch Uro-Oncology Study Group; Non-Financial Interests, Principal Investigator, Co-PI: Prospective Bladder Cancer Infrastructure (Netherlands); Non-Financial Interests, Leadership Role: Castration-resistant Prostate Cancer Registry. All other authors have declared no conflicts of interest.