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Clinical Studies

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

British Journal of Cancer volume 128, pages 21–29 (2023)Cite this article

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Abstract

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.

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Fig. 1: Trial schema.
Fig. 2: Prostate-specific antigen and radiographic responses waterfall plots.
Fig. 3: Kaplan–Meier curves for overall survival and progression-free survival.

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Data availability

The datasets generated and/or analysed during this study are available from the corresponding author upon reasonable request.

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Acknowledgements

Study was carried out by Pivotal CRO. Statistical analyses were performed by Tania San José. The Sponsor of the study was APRO (Associació per la recerca oncològica, Spanish Oncology Research Group).

Funding

Funding for this study was jointly provided through an unrestricted educational grant from Pfizer, Inc, New York, NY, USA and Merck KGaA, Darmstadt, Germany, as part of an alliance between Merck (CrossRef Funder ID: 10.13039/100009945) and Pfizer. Pfizer and Merck reviewed the manuscript for medical accuracy only before journal submission. The authors are fully responsible for the content of this manuscript, and the views and opinions described in the publication reflect solely those of the authors.

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Authors and Affiliations

  1. Medical Oncology Department, Hospital del Mar-CIBERONC, IMIM Research Institute, Barcelona, Spain

    Alejo Rodriguez-Vida, Alex Corbera, Mayra Orrillo, Alejandro Rios-Hoyo, Alvaro Taus, Maria Martinez-Garcia & Joaquim Bellmunt

  2. Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    Pablo Maroto & Cristina Martin

  3. Medical Oncology Department, Catalan Institute of Oncology - Badalona, B-ARGO Group, IGTP, Barcelona, Spain

    Albert Font

  4. Medical Oncology Department, Hospital Clínic, Barcelona, Spain

    Begoña Mellado & Oscar Reig

  5. Translational Genomics and Targeted Therapeutics in Solid Tumors Lab, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Begoña Mellado & Oscar Reig

  6. Uro-Oncology Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain

    Begoña Mellado & Oscar Reig

  7. Department of Medicine, University of Barcelona, Barcelona, Spain

    Begoña Mellado & Oscar Reig

  8. Medical Oncology Department, Hospital de Mataró, Barcelona, Spain

    Rosa Querol

  9. Clinical Trials Unit, Hospital del Mar, Barcelona, Spain

    Laia Cano, Judith Alonso, Gemma Martinez & Susana Galtes

  10. Pathology Department, Hospital del Mar, Barcelona, Spain

    Nuria Juanpere

  11. Pivotal SLU Clinical Research Organization, Madrid, Spain

    Oscar Juan

  12. Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

    Joaquim Bellmunt

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Contributions

All authors conceived and/or designed the work that led to the submission, acquired data and/or played an important role in interpreting the results; drafted or revised the manuscript; approved the final version and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Joaquim Bellmunt.

Ethics declarations

Ethics approval and consent to participate

The study was carried out with the approval of the Institutional Ethics committee of all participating institutions. The study was conducted in accordance with the ethical principles pronounced in the Declaration of Helsinki (Amendment 64th of the World Medical Association General Assembly, Fortaleza, Brazil, October 2013). This study was registered at the European Union Drug Regulating Authorities Clinical Trials Database as EudraCT Number 2017-004552-39.

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A signed informed consent was obtained from each participant prior to any study procedure.

Competing interests

Dr. JB reports serving in an advisory role to Genentech, MSD, Pfizer, GSK, BMS, AstraZeneca, Pierre-Fabre, Sanofi Aventis, Astellas, OncoGenex, and Janssen; receiving honoraria or travel expenses from Pfizer, MSD, GSK, Novartis, Pierre-Fabre, Astellas, and BMS; and receiving research funding from Takeda, Pfizer, Novartis, and Sanofi Aventis. Dr. AR-V reports serving in an advisory role for MSD, Pfizer, BMS, Astellas, Janssen, Bayer, Clovis and Roche; receiving honoraria or travel expenses from Pfizer, MSD, Astellas, BMS, Janssen, AstraZeneca, Roche, Bayer, and Sanofi Aventis; and receiving research funding from Takeda, Pfizer, and Merck. Dr. PM reports serving in advisory board for Pfizer, Ipsen, and BMS. Dr. AF reports serving in an advisory role to Janssen, Astellas, Sanofi, Eusa; and receiving research funding from AstraZeneca. Dr. BM has received consulting fees from Pfizer, Roche, AstraZeneca, Bayer, Astellas Pharma, and Janssen, support for attending meetings or travel from Janssen-Cilag; and other financial or non-financial interests from Roche, Janssen, and Bayer. Dr. AT reports personal fees and non-financial support from Roche, BMS, MSD, GSK, AstraZeneca and Pfizer. Dr. AC reports receiving honoraria or travel expenses from Astellas, BMS, Janssen, and Merck. Dr. RQ repots Personal fees and non-financial support from Merck, Sanofi Aventis, Roche, Pfizer, Jansen, Amgen and Astellas. Dr. OJ declares being an employee of Pivotal SLU. Dr. MM-G reports serving in an advisory role for Roche, Seagen and Pierre-Fabre; receiving honoraria or travel expenses from Roche and Pfizer. Dr. NJ reports serving in an advisory role for AstraZeneca; and receiving honoraria or travel expenses from Roche and MSD. Dr. Oscar Reig, Dr. AR-H, Dr. MO and Dr. CM report no competing interests.

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Rodriguez-Vida, A., Maroto, P., Font, A. et al. 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 128, 21–29 (2023). https://doi.org/10.1038/s41416-022-01991-4

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