579MO - CheckMate 9KD cohort A2 final analysis: Nivolumab (NIVO) + rucaparib for chemotherapy (CT)-naïve metastatic castration-resistant prostate cancer (mCRPC)

Background

CheckMate 9KD is a phase II, multi-cohort trial of NIVO (anti–PD-1) combined with rucaparib, docetaxel, or enzalutamide for mCRPC. We report results for cohort A2, assessing NIVO + rucaparib for CT-naïve mCRPC.

Methods

In cohort A2, unselected patients (pts) with CT-naïve mCRPC, ongoing ADT, prior abiraterone and/or enzalutamide for mCRPC, and no prior PARP inhibitors received NIVO 480 mg Q4W + rucaparib 600 mg BID until disease progression/unacceptable toxicity (NIVO dosing ≤ 2 y). Coprimary endpoints were objective response rate (ORR) per PCWG3 criteria and prostate-specific antigen response rate (PSA-RR) in all treated pts and pts with homologous recombination deficiency positive (HRD+) tumors; HRD status was determined before enrollment. Secondary endpoints included radiographic progression-free survival (rPFS), overall survival (OS), and safety.

Results

Of 71 treated pts, median age 73 y (range, 51–87 y), 23.9% had visceral metastases and 54.9% had measurable disease. Median treatment duration was 4.6 mo for NIVO and 5.5 mo for rucaparib; median follow-up was 17.5 mo. The table summarizes efficacy results, and shows better outcomes for HRD+ vs HRD–/not evaluable tumors. Any-grade treatment-related AEs (TRAEs) occurred in 90.1% of pts, most commonly nausea (40.8%) and anemia (32.4%). Grade ≥ 3 TRAEs occurred in 50.7% of pts, most commonly anemia (14.1%) and increased ALT (12.7%). TRAEs led to discontinuation in 23.9% of pts. No treatment-related deaths were reported. Table: 579MO

^aPts with measurable disease at baseline; ^b≥ 50% PSA reduction from baseline.^cPts with a baseline and ≥ 1 post-baseline PSA assessment. NE, not estimable.

Conclusions

NIVO + rucaparib is active in pts with HRD+ CT-naïve mCRPC. Longer follow-up is needed to better characterize clinical benefits of adding NIVO to rucaparib for this population. Clinical activity in pts with HRD– tumors was limited. The safety profile of NIVO + rucaparib was as expected based on the individual components, with no new safety signals. Ongoing biomarker analyses will assess the impact of specific HRD mutations on treatment efficacy.

Clinical trial identification

NCT03338790.

Editorial acknowledgement

Writing and editorial assistance was provided by Richard Daniel, PhD, of Parexel, funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

D.P. Petrylak: Financial Interests, Personal, Other, Consultant Fees: Ada Cap (Advanced Accelerator Applications) Amgen, Astellas, AstraZeneca, Bayer, Bicycle Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Clovis Oncology, Eli Lilly, Exelixis, Incyte, Janssen, Mirati, Monopteros, Pfizer, Pharmacyclics, Roche, Se; Financial Interests, Personal, Stocks/Shares: Bellicum (Sold 7/2020), Tyme (sold 10/2019); Financial Interests, Institutional, Invited Speaker: Ada Cap (Advanced Accelerator Applications), Agensys Inc, Astellas, AstraZeneca, Bayer, BioXcel Therapeutics, Bristol Myers Squibb, Clovis Oncology, Eisai, Eli Lilly, Endocyte, Genentech, Innocrin, MedImmune, Medivation, Merck, Mirati, Novartis, Pfizer. J.L. Perez-Gracia: Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Institutional, Principal Investigator, Local PI: Amgen; Financial Interests, Institutional, Principal Investigator, Local PI: BMS; Financial Interests, Personal, Funding: Ipsen; Non-Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Seattle Genetics; Other, Personal, Other, Travel Support: Roche. L. Lacombe: Financial Interests, Institutional, Invited Speaker, Clinical studies: Astra-Zeneca; Financial Interests, Institutional, Invited Speaker, Clinical studies: BMS; Financial Interests, Institutional, Invited Speaker, Clinical studies: Merck; Financial Interests, Institutional, Invited Speaker, Clinical studies: Pfizer; Financial Interests, Institutional, Invited Speaker, Clinical studies: Telix; Financial Interests, Institutional, Invited Speaker, Clinical studies: Janssen; Financial Interests, Institutional, Invited Speaker, Clinical studies: Astellas; Financial Interests, Institutional, Invited Speaker, null: Myovant; Financial Interests, Institutional, Invited Speaker, Clinical studies: Hoffmann- La Roche; Financial Interests, Institutional, Invited Speaker, Clinical studies: Medimmune; Financial Interests, Institutional, Invited Speaker, Clinical studies: Bayer; Financial Interests, Institutional, Invited Speaker, Clinical studies: Sanofi. D.A. Bastos: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Invited Speaker: AztraZeneca; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Janssen. H. Mahammedi: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Sanofi; Non-Financial Interests, Personal, Principal Investigator: BMS; Non-Financial Interests, Personal, Principal Investigator: Janssen; Non-Financial Interests, Personal, Principal Investigator: MSD; Non-Financial Interests, Personal, Principal Investigator: Pfizer; Non-Financial Interests, Personal, Principal Investigator: Roche; Non-Financial Interests, Personal, Principal Investigator: Sanofi. E.M. Kwan: Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Writing Engagements: Research Review; Financial Interests, Institutional, Principal Investigator, Local PI ARCHES study: Astellas Pharma; Financial Interests, Institutional, Principal Investigator, Local PI PROFOUND: AstraZeneca; Financial Interests, Institutional, Principal Investigator, Local PI CheckMae 9KD: BMS; Financial Interests, Institutional, Invited Speaker, Coordinating PI ICE-PAC: Merck KGaA; Financial Interests, Institutional, Invited Speaker, Local PI TALAPRO: Pfizer; Non-Financial Interests, Personal, Principal Investigator, ARCHES: Astellas Pharma; Non-Financial Interests, Personal, Principal Investigator, PROFOUND: AstraZeneca; Non-Financial Interests, Personal, Principal Investigator, CheckMate 9KD: BMS; Non-Financial Interests, Personal, Principal Investigator, ICE-PAC: Merck KGaA; Non-Financial Interests, Personal, Principal Investigator, TALAPRO: Pfizer. S. Zschäbitz: Financial Interests, Institutional, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Other, Travel Grant: Celgene; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Institutional, Advisory Board: EUSA; Financial Interests, Institutional, Invited Speaker: Merck; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Sanofi Aventis; Financial Interests, Principal Investigator, Local PI: Astellas; Financial Interests, Principal Investigator, Coordinating PI: BMS; Financial Interests, Principal Investigator, Local PI: Calithera Biosciences; Financial Interests, Principal Investigator, Local PI: Clovis Oncology; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Principal Investigator, Local PI: Exelixis; Financial Interests, Principal Investigator, Local PI: Pfizer; Financial Interests, Principal Investigator, Local PI: Roche; Non-Financial Interests, Personal, Member: ASCO; Non-Financial Interests, Personal, Member: DGHA. A.J. Armstrong: Financial Interests, Personal, Other, Consultant: Astellas; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: Dendreon; Financial Interests, Personal, Invited Speaker: Forma; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Institutional, Principal Investigator, Local PI: Amgen; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Astellas; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Bayer; Financial Interests, Institutional, Principal Investigator, Local PI: Beigene; Financial Interests, Institutional, Principal Investigator, Coordinating PI: BMS; Financial Interests, Institutional, Member, Steering Committee Member: Dendreon; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Janssen; Financial Interests, Institutional, Principal Investigator, Local PI: Merck; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Pfizer. R.K. Pachynski: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Dendreon; Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Invited Speaker: Genentech/Roche; Financial Interests, Personal, Advisory Board: Genomic Health; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Jounce; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Member, Steering Committee Member: BMS; Financial Interests, Institutional, Funding: Janssen; Financial Interests, Institutional, Funding: Pharmacylics; Financial Interests, Personal, Invited Speaker: Sanofi; Non-Financial Interests, Principal Investigator: BMS; Non-Financial Interests, Principal Investigator: ESSA; Non-Financial Interests, Principal Investigator: Janssen; Non-Financial Interests, Principal Investigator: Merck; Non-Financial Interests, Principal Investigator: Pfizer/EMD Serono. J.C. Goh: Financial Interests, Personal, Advisory Board, Prior member of BMS RCC Advisory Board: BMS; Non-Financial Interests, Personal, Principal Investigator, Local PI for CheckMate 9KD trial, CheckMate- 7DX CheckMate 9ER: BMS. M. Burotto: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Roche. G. Gravis: Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Advisory Board: Janssen; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: Alliance Merck-Pfizer; Financial Interests, Institutional, Advisory Board: AAA; Financial Interests, Institutional, Invited Speaker: Astellas; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Invited Speaker: Janssen; Financial Interests, Institutional, Invited Speaker: Amgen; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Invited Speaker: Sanofi; Financial Interests, Institutional, Funding: Janssen; Financial Interests, Institutional, Principal Investigator, Coordinating PI: BMS; Financial Interests, Institutional, Other, Travel accommodations expenses: BMS; Financial Interests, Institutional, Other, Travel accommodations expenses: Janssen; Financial Interests, Institutional, Other, Travel accommodations expenses: Sanofi. S.L. McCune: Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Institutional, Principal Investigator, Local PI for clinical trials sponsored by BMS: BMS; Financial Interests, Institutional, Principal Investigator, Local PI on Merck studies: Merck; Financial Interests, Institutional, Principal Investigator, Local PI on ompany sponsored clinical trials: Roche Genentech. J.C. Vázquez Limón: Financial Interests, Institutional, Full or part-time Employment, Attending physician and chief of oncology service: Hospital Civil de Guadalajara \"Fray Antonio Alcalde; Financial Interests, Personal and Institutional, Principal Investigator, Local PI: AstraZeneca; Financial Interests, Personal and Institutional, Principal Investigator, Local PI: BMS; Financial Interests, Personal and Institutional, Principal Investigator, Local PI: Europharma; Financial Interests, Personal and Institutional, Principal Investigator, Local PI: Janssen; Financial Interests, Personal and Institutional, Principal Investigator, Local PI: MSD; Financial Interests, Personal and Institutional, Principal Investigator, Local PI: Novartis. F. Saad: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Myovant; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Institutional, Principal Investigator, Local PI: Amgen; Financial Interests, Institutional, Principal Investigator, Local PI: Astellas; Financial Interests, Institutional, Principal Investigator, Local PI: Bayer; Financial Interests, Institutional, Principal Investigator, Local PI: BMS; Financial Interests, Institutional, Principal Investigator, Local PI: Janssen; Financial Interests, Institutional, Principal Investigator, Local PI: Novartis; Financial Interests, Institutional, Principal Investigator, Local PI: Pfizer; Financial Interests, Institutional, Principal Investigator, Local PI: Sanofi. N.P. Amin: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. J. Li: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. K. Unsal-Kacmaz: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. K. Fizazi: Financial Interests, Institutional, Advisory Board: AAA; Financial Interests, Institutional, Advisory Board: Astellas; Financial Interests, Institutional, Invited Speaker: Astellas; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Advisory Board: Bayer; Financial Interests, Institutional, Invited Speaker: Bayer; Financial Interests, Personal, Advisory Board: Curevac; Financial Interests, Institutional, Advisory Board: Janssen; Financial Interests, Institutional, Invited Speaker: Janssen; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: Orion; Financial Interests, Institutional, Invited Speaker: Sanofi; Financial Interests, Institutional, Research Grant, Trial chair: Bayer; Financial Interests, Institutional, Research Grant, Trial chair: BMS; Financial Interests, Institutional, Research Grant, Trial chair: Janssen; Financial Interests, Institutional, Research Grant, Trial chair: MSD; Financial Interests, Institutional, Research Grant, Trial chair: Orion; Financial Interests, Institutional, Research Grant, Trial chair: Pfizer. All other authors have declared no conflicts of interest.