Safety and efficacy of avelumab plus carboplatin in patients with metastatic castration-resistant prostate cancer in an open-label Phase Ib study

Br J Cancer. 2023 Jan;128(1):21-29. doi: 10.1038/s41416-022-01991-4. Epub 2022 Oct 26.


Background: Single-agent PD-1/PD-L1 inhibitors have shown limited efficacy in unselected mCRPC. The evidence of a survival benefit with sipuleucel-T and ipilimumab, provides a rationale to study further increasing immunogenicity in mCRPC through combinations.

Methods: Safety and efficacy avelumab plus carboplatin was investigated in a single-arm Phase Ib study in mCRPC, progressing to at least one taxane and one androgen-receptor inhibitor. The primary endpoint was safety. Secondary endpoints included PSA/radiographic responses, progression-free survival (PFS) and overall survival (OS). Germline/somatic mutation analysis was performed.

Results: In total, 26 patients were included. Patients were heavily pretreated: 76.9% received ≥3 and 42.3% ≥4 prior lines. A DNA damage repair (DDR) alteration was found in three patients (11.5%). The safety profile was acceptable with 73% Grade 3-4 treatment-related adverse events. PSA response rate ≥50% was seen in 7.7% of patients. The objective response rate was 17.6%, including one complete response (5.9%). Two of these responders had a known DDR alteration (one BRCA2, one ATM). The median response duration was 6 months. Median radiographic PFS was 6.6 months (95% CI 4.28-9.01), and median OS 10.6 months (95% CI 6.68-NR).

Conclusions: Avelumab plus carboplatin has an acceptable safety profile and was associated with a prolonged OS given the heavily pretreated population.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / adverse effects
  • Carboplatin / adverse effects
  • Humans
  • Male
  • Prostate-Specific Antigen
  • Prostatic Neoplasms, Castration-Resistant* / drug therapy
  • Prostatic Neoplasms, Castration-Resistant* / genetics


  • Carboplatin
  • avelumab
  • Prostate-Specific Antigen
  • Antibodies, Monoclonal, Humanized