Efficacy and Safety of Nivolumab in Combination With Docetaxel in Men With Metastatic Castration-Resistant Prostate Cancer in CheckMate 9KD

Date 29 September 2019
Event ESMO 2019 Congress
Session Poster Discussion – Genitourinary tumours, prostate
Presenter Karim Fizazi
Citation Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz394
Authors K. Fizazi1, P. Gonzalez Mella2, D. Castellano3, J.N. Minatta4, A. Rezazadeh Kalebasty5, D. Shaffer6, J.C. Vazquez Limon7, A.J. Armstrong8, H.M. Sanchez Lopez9, B. Sharkey10, A. Saci11, J. Li12, X. Wang12, M. Ciprotti13, P. Sathyanarayana14, F. Saad15, D.P. Petrylak16, M.M. Retz17, R.K. Pachynski18, C. Drake19
  • 1Oncology, Gustave Roussy, University of Paris Sud, 91400 - Villejuif/FR
  • 2Department Of Medical Oncology, Instituto Oncológico, Universidad de Valparaíso, 2520000 - Viña del Mar/CL
  • 3Medical Oncology, Hospital Universitario 12 de Octubre, 28041 - Madrid/ES
  • 4Oncology, Hospital Italiano de Buenos Aires, 1181 - Buenos Aires/AR
  • 5Medical Oncology, Norton Cancer Institute, 402021840 - Louisville/US
  • 6Medical Oncology, New York Oncology Hematology, 12208 - Albany/US
  • 7Medical Oncology, Instituto Jalisciense de Cancerología, 44280 - Guadalajara/MX
  • 8Duke Cancer Institute For Prostate And Urologic Cancers, Duke University, Durham/US
  • 9Department Of Urological Oncology, Hospital Regional de Alta Especialidad del Bajío, 37660 - Guanajuato/MX
  • 10Global Biometrics Sciences, Bristol Myers Squibb, 08540 - Princeton/US
  • 11Biomarkers, Bristol-Myers Squibb, Princeton/US
  • 12Translational Bioinformatics, Bristol Myers Squibb, 08540 - Princeton/US
  • 13Oncology Clinical Development, Bristol-Myers Squibb, UB8 1DH - Uxbridge/GB
  • 14Oncology Clinical Development, Bristol-Myers Squibb, 088540 - Princeton/US
  • 15Urology, Centre Hospitalier de l’Université de Montréal/CRCHUM, H2X 3J4 - Montreal/CA
  • 16Medical Oncology, Yale School of Medicine, 06510 - New Haven/US
  • 17Department Of Urology, Rechts Der Isar Medical Center, Technical University of Munich, 80333 - Munich/DE
  • 18Department Of Medicine, Division Of Oncology, Washington University School of Medicine, 63110 - St. Louis/US
  • 19Medical Oncology, Columbia University Medical Center, 10032 - New York/US

Abstract

Background

The antitumor activity of programmed death-1 (PD-1)/PD-1 ligand 1 (PD-L1) inhibition alone is limited in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). Combining immunotherapy with standard-of-care chemotherapy could improve outcomes in mCRPC. We report interim analysis results for the nivolumab + docetaxel (NIVO+DOCE) treatment arm from CheckMate 9KD.

Methods

CheckMate 9KD is a phase II study of NIVO in combination with DOCE, rucaparib, or enzalutamide. Eligible pts had confirmed metastatic adenocarcinoma of the prostate, ongoing androgen deprivation therapy, and evaluable tumor biopsy. Pts assigned to NIVO+DOCE (chemotherapy-naïve and received ≤2 prior second-generation hormonal therapies) received NIVO 360 mg every 3 weeks + DOCE 75 mg/m2 every 3 weeks + prednisone 5 mg twice daily for ≤10 cycles followed by NIVO 480 mg every 4 weeks alone until disease progression or unacceptable toxicity (up to 2 years). Coprimary endpoints were objective response rate (ORR) and prostate-specific antigen response rate (PSA-RR; defined as ≥ 50% PSA reduction from baseline). Secondary endpoints included radiographic progression-free survival (rPFS), and safety/tolerability in all treated pts. Association of biomarkers with efficacy was an exploratory endpoint.

Results

This interim analysis included 41 pts in the NIVO+DOCE arm with a minimum follow-up of 28 weeks, of whom 19 (46.3%) had measurable disease. At the time of the analysis, 24 (58.5%) had discontinued study treatment. ORR in pts with measurable disease was 36.8% (95% confidence interval [CI], 16.3–61.6) with 1 complete response and 6 partial responses. Confirmed PSA-RR was 46.3% (95% CI, 30.7–62.6). Median rPFS was 8.2 months (95% CI, 6.6–not estimable). The 6-month rPFS rate was 71.5%. Any-grade and grade 3/4 treatment-related adverse events occurred in 92.7% and 48.8% of pts, respectively. Associations of biomarkers are also evaluated.

Conclusions

The combination of NIVO+DOCE showed encouraging clinical activity in pts with mCRPC, with a safety profile consistent with those of the individual agents. A phase III trial is warranted to further evaluate NIVO+DOCE in mCRPC.

Clinical trial identification

NCT03338790.

Editorial acknowledgement

Professional medical writing assistance was provided by Nicolette Belletier, PhD, of Parexel, and funded by Bristol-Myers Squibb.

Legal entity responsible for the study

Bristol-Myers Squibb.

Funding

Bristol-Myers Squibb and Ono Pharmaceutical Company Limited.

Disclosure

K. Fizazi: Advisory / Consultancy: Janssen; Advisory / Consultancy: Astellas; Advisory / Consultancy: Bayer; Advisory / Consultancy: Orion. A. Rezazadeh Kalebasty: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Genentech; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Exelexis; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: AZ; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Eisai; Research grant / Funding (institution): Macrogenics; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas; Research grant / Funding (institution): Beyond Spring; Research grant / Funding (institution): Bioclin/Rainier Therapeutics; Research grant / Funding (institution): Clovis; Research grant / Funding (institution): Bavarian; Research grant / Funding (institution): Nordic; Research grant / Funding (institution): Seattle Genetics; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Shareholder / Stockholder / Stock options: ECOM; Honoraria (self), Speaker Bureau / Expert testimony: Sanofi; Honoraria (self), Speaker Bureau / Expert testimony: Amgen; Travel / Accommodation / Expenses: Prometheus Labs. J.C. Vazquez Limon: Non-remunerated activity/ies, Personal Fees and non-financial support: AstraZeneca; Non-remunerated activity/ies, Non-financial support: Merck; Non-remunerated activity/ies, Personal fees: Roche; Non-remunerated activity/ies, Personal fees: Bristol-Myers Squibb. A.J. Armstrong: Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Janssen; Advisory / Consultancy, Research grant / Funding (institution): Pfizer/Astellas; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Dendreon; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Byer; Research grant / Funding (institution): Constellation; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy: Clovis. B. Sharkey: Full / Part-time employment: Bristol-Myers Squibb. A. Saci: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. J. Li: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. X. Wang: Full / Part-time employment: Bristol-Myers Squibb. M. Ciprotti: Full / Part-time employment: Bristol-Myers Squibb. P. Sathyanarayana: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. F. Saad: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Astellas; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Janssen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bayer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer. D.P. Petrylak: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Bellicum; Research grant / Funding (institution): Clovis; Advisory / Consultancy, Research grant / Funding (institution): Dendreon; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Endocyte ; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Ferring; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Innocrin; Advisory / Consultancy, Research grant / Funding (institution): Johnson and Johnson; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Millineum; Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Progenics; Research grant / Funding (institution): Roche Labatories; Advisory / Consultancy, Research grant / Funding (institution): Sanofi Aventis; Research grant / Funding (institution): Sotio; Speaker Bureau / Expert testimony, Research grant / Funding (institution), Shareholder / Stockholder / Stock options: Tyme Pharmaceuticals. R.K. Pachynski: Advisory / Consultancy, Research grant / Funding (institution): BMS; Speaker Bureau / Expert testimony: Dendreon; Advisory / Consultancy: EMD Serono/Pfizer; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Genentech/Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Genomic Health; Research grant / Funding (institution): Janssen; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi; Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy: Jounce Therapeutics. C. Drake: Advisory / Consultancy, Research grant / Funding (institution), Shareholder / Stockholder / Stock options: Compugen; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy, Research grant / Funding (institution): Janssen Oncology; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Astellas Medivation; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Tizona Therapeutics; Advisory / Consultancy: Merck; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: F-Star; Advisory / Consultancy, Shareholder / Stockholder / Stock options: KLEO; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Harpoon; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Shattuck Labs; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Werewolf; Advisory / Consultancy: Genocea; Advisory / Consultancy: Sanofi Aventis; Advisory / Consultancy, Licensing / Royalties: Amplimmune; Advisory / Consultancy, Licensing / Royalties: BMS; Advisory / Consultancy: EMD. All other authors have declared no conflicts of interest.