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CheckMate 9KD cohort A1 final analysis: Nivolumab (NIVO) + rucaparib for post-chemotherapy (CT) metastatic castration-resistant prostate cancer (mCRPC)

Authors :
Marc-Oliver Grimm
Mauricio Burotto
Juan Carlos Vazquez Limon
David R. Shaffer
Daniel P. Petrylak
Stefanie Zschaebitz
Gwenaelle Gravis
Karim Fizazi
Russell K. Pachynski
Daniel Castellano
Margitta Retz
Jia Li
Fred Saad
Neha P. Amin
Keziban Unsal-Kacmaz
Aude Flechon
Xuya Wang
Steven L. McCune
Jeffrey C. Goh
Source :
Journal of Clinical Oncology. 39:5044-5044
Publication Year :
2021
Publisher :
American Society of Clinical Oncology (ASCO), 2021.

Abstract

5044 Background: CheckMate 9KD is a phase 2 trial of NIVO (anti-PD-1) combined with either rucaparib, docetaxel, or enzalutamide for mCRPC. PARP inhibitors, like rucaparib, increase cellular DNA damage, particularly in tumors with DNA repair defects, leading to genomic instability and cell death. This DNA damage promotes immune priming and adaptive PD-L1 upregulation. Consequently, dual PD-(L)1 and PARP inhibition is a plausible therapeutic strategy for mCRPC. We report final results for cohort A1 (NIVO + rucaparib for post-CT mCRPC) of CheckMate 9KD. Methods: Cohort A1 enrolled patients (pts) with post-CT mCRPC (1–2 prior taxane regimens), ongoing ADT, ≤ 2 prior novel hormonal therapies (abiraterone, enzalutamide, etc) for mCRPC, and no prior PARP inhibitor treatment. Pts received NIVO 480 mg Q4W + rucaparib 600 mg BID until disease progression/unacceptable toxicity (NIVO dosing limited to 2 yrs). Coprimary endpoints: objective response rate (ORR) per PCWG3 criteria and prostate-specific antigen response rate (PSA-RR; ≥ 50% PSA reduction) in all treated pts and pts with homologous recombination deficiency positive (HRD+) tumors, determined before enrollment. Secondary endpoints included radiographic progression-free survival (rPFS), overall survival (OS), and safety. Results: Of 88 treated pts, median age 66 yrs (range, 46–85), 34.1% had visceral metastases and 65.9% had measurable disease. Median follow-up was 11.9 mo. Pts had a median of 4.5 NIVO doses and 3.8 mo of rucaparib. The table summarizes primary and key secondary efficacy results, and shows better outcomes for HRD+ vs HRD–/not evaluable (NE) tumors. In pts with BRCA2 mutations, confirmed ORR was 37.5% (3/8 pts) and confirmed PSA-RR was 45.5% (5/11 pts). Any-grade treatment-related AEs (TRAEs) occurred in 93.2% of pts, most commonly nausea (40.9%) and fatigue (33.0%). Grade ≥ 3 TRAEs occurred in 54.5% of pts, most commonly anemia (20.5%) and neutropenia (10.2%). TRAEs led to discontinuation in 27.3% of pts. One pt had a stroke, considered related to rucaparib by the investigator, after 28 days on rucaparib and 2 NIVO doses and died 2 months later due to post-thrombolysis hematoma. Conclusions: NIVO + rucaparib is active in pts with HRD+ post-CT mCRPC, although the trial design and short follow-up limit assessment of benefits of the combination vs individual components. Pts with HRD– tumors did not appear to benefit from either drug. No new safety signals were observed with NIVO + rucaparib. Additional biomarker analyses are ongoing. Clinical trial information: NCT03338790. [Table: see text]

Details

ISSN :
15277755 and 0732183X
Volume :
39
Database :
OpenAIRE
Journal :
Journal of Clinical Oncology
Accession number :
edsair.doi...........8140c68d5ffaa5dc2fef55e723818b2f
Full Text :
https://doi.org/10.1200/jco.2021.39.15_suppl.5044