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

Padmanee Sharma, Russell K. Pachynski, Vivek Narayan, Aude Fléchon, Gwenaelle Gravis, Matthew D. Galsky, Hakim Mahammedi, Akash Patnaik, Sumit K. Subudhi, Marika Ciprotti, Burcin Simsek, Abdel Saci, Yanhua Hu, G. Celine Han, Karim Fizazi

Research output: Contribution to journalArticlepeer-review

98 Scopus citations

Abstract

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. From a preliminary phase II clinical trial on metastatic castration-resistant prostate cancer with anti-CTLA-4 plus anti-PD-1, Sharma et al. report ORR of 25% and 10%, median rPFS of 5.5 and 3.8 months, and median OS of 19.0 and 15.2 months in pre- and post-chemotherapy patients. Additional analyses with modified dosing are needed to optimize safety.

Original languageEnglish
Pages (from-to)489-499.e3
JournalCancer Cell
Volume38
Issue number4
DOIs
StatePublished - Oct 12 2020

Keywords

  • DNA damage repair
  • biomarkers
  • clinical trial
  • immunotherapy
  • ipilimumab
  • metastatic castration-resistant prostate cancer
  • nivolumab
  • tumor mutational burden

Fingerprint

Dive into the research topics of 'Nivolumab Plus Ipilimumab for Metastatic Castration-Resistant Prostate Cancer: Preliminary Analysis of Patients in the CheckMate 650 Trial'. Together they form a unique fingerprint.

Cite this