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Nivolumab Plus Ipilimumab for Metastatic Castration-Resistant Prostate Cancer: Preliminary Analysis of Patients in the CheckMate 650 Trial

Highlights


  • We found 25% ORR in pre-chemotherapy cohort 1 and 10% ORR in post-chemotherapy cohort 2
  • We report 5.5 and 3.8 months median rPFS and 19.0 and 15.2 months median OS
  • Exploratory analyses identify potential biomarkers of response
  • Study expansion is needed to assess other dosing regimens

Summary 

Metastatic castration-resistant prostate cancer (mCRPC) is immunologically “cold” and predominantly resistant to immune checkpoint therapy due to few tumor-infiltrating T cells. Ipilimumab (anti-CTLA-4) or anti-PD-1/PD-L1 monotherapy failed to show a significant benefit. Although the PD-1/PD-L1 pathway is minimally expressed in prostate tumors, we previously demonstrated that PD-1/PD-L1 expression increases as a compensatory inhibitory pathway in parallel with an ipilimumab-induced increase in tumor-infiltrating T cells. Here, we report the largest trial to date in mCRPC with anti-CTLA-4 plus anti-PD-1 (nivolumab 1 mg/kg plus ipilimumab 3 mg/kg; CheckMate 650, NCT02985957). With median follow-ups of 11.9 and 13.5 months in cohorts 1 (pre-chemotherapy; n = 45) and 2 (post-chemotherapy; n = 45), objective response rate was 25% and 10%, and median overall survival was 19.0 and 15.2 months, respectively. Four patients, two in each cohort, had complete responses. Exploratory studies identify potential biomarkers of response. Grade 3–4 treatment-related adverse events have occurred in ∼42%–53% of patients, with four treatment-related deaths. Therefore, dose/schedule modifications have been implemented.

Graphical Abstract

checkmate650trial.png
Written by: Padmanee Sharma, 1 Russell K. Pachynski,2 Vivek Narayan,3 Aude Fléchon,4 Gwenaelle Gravis,5 Matthew D. Galsky,6 Hakim Mahammedi,7 Akash Patnaik,8 Sumit K. Subudhi,9 Marika Ciprotti,10 Burcin Simsek,10 Abdel Saci,10 Yanhua Hu,10 G. Celine Han,10 Karim Fizazi11

  1. Department of Genitourinary Medical Oncology, MD Anderson Cancer Center, University of Texas
  2. Division of Oncology, Washington University School of Medicine
  3. Abramson Cancer Center, University of Pennsylvania
  4. Department of Medical Oncology, Centre Léon Bérard
  5. Department of Medical Oncology, Institut Paoli-Calmettes Aix-Marseille Université
  6. Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai
  7. Department of Medical Oncology, Centre Jean Perrin
  8. Department of Medical Oncology, The University of Chicago Medicine
  9. Department of Genitourinary Medical Oncology, MD Anderson Cancer Center, University of Texas
  10. Bristol Myers Squibb
  11. Department of Cancer Medicine, Gustave Roussy, University of Paris Saclay
Source: Padmanee Sharma et al. Nivolumab Plus Ipilimumab for Metastatic Castration-Resistant Prostate Cancer: Preliminary Analysis of Patients in the CheckMate 650 Trial. 10, Sept 2020. DOI: https://doi.org/10.1016/j.ccell.2020.08.007.



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