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Open Access 01-04-2024 | Prostate Cancer | Research

A phase 2 study of AZD4635 in combination with durvalumab or oleclumab in patients with metastatic castration-resistant prostate cancer

Authors: Gerald S. Falchook, James Reeves, Sunil Gandhi, David R. Spigel, Edward Arrowsmith, Daniel J. George, Janet Karlix, Gayle Pouliot, Maureen M. Hattersley, Eric T. Gangl, Gareth D. James, Jeff Thompson, Deanna L. Russell, Bhavickumar Patel, Rakesh Kumar, Emerson Lim

Published in: Cancer Immunology, Immunotherapy | Issue 4/2024

Abstract

Background

Inhibition of the adenosine 2A receptor (A_2AR) diminishes the immunosuppressive effects of adenosine and may complement immune-targeting drugs. This phase 2 study evaluated the A_2AR antagonist AZD4635 in combination with durvalumab or oleclumab in patients with metastatic castration-resistant prostate cancer.

Methods

Patients with histologically/cytologically confirmed disease progressing within 6 months on ≥ 2 therapy lines were randomly assigned to either Module 1 (AZD4635 + durvalumab) or Module 2 (AZD4635 + oleclumab). Primary endpoints were objective response rate per RECIST v1.1 and prostate-specific antigen (PSA) response rate. Secondary endpoints included radiological progression-free survival (rPFS), overall survival, safety, and pharmacokinetics.

Results

Fifty-nine patients were treated (Module 1, n = 29; Module 2, n = 30). Median number of prior therapies was 4. One confirmed complete response by RECIST (Module 1) and 2 confirmed PSA responses (1 per module) were observed. The most frequent adverse events (AEs) possibly related to AZD4635 were nausea (37.9%), fatigue (20.7%), and decreased appetite (17.2%) in Module 1; nausea (50%), fatigue (30%), and vomiting (23.3%) in Module 2. No dose-limiting toxicities or treatment-related serious AEs were observed. In Module 1, AZD4635 geometric mean trough concentration was 124.9 ng/mL (geometric CV% 69.84; n = 22); exposures were similar in Module 2. In Modules 1 and 2, median (95% CI) rPFS was 2.3 (1.6 –3.8) and 1.5 (1.3– 4.0) months, respectively. Median PFS was 1.7 versus 2.3 months for patients with high versus low blood-based adenosine signature.

Conclusion

In this heavily pretreated population, AZD4635 with durvalumab or oleclumab demonstrated minimal antitumor activity with a manageable safety profile. Clinical Trial.gov identifier: NCT04089553.

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Title: A phase 2 study of AZD4635 in combination with durvalumab or oleclumab in patients with metastatic castration-resistant prostate cancer
Authors: Gerald S. Falchook
James Reeves
Sunil Gandhi
David R. Spigel
Edward Arrowsmith
Daniel J. George
Janet Karlix
Gayle Pouliot
Maureen M. Hattersley
Eric T. Gangl
Gareth D. James
Jeff Thompson
Deanna L. Russell
Bhavickumar Patel
Rakesh Kumar
Emerson Lim
Publication date: 01-04-2024
Publisher: Springer Berlin Heidelberg
Keywords: Prostate Cancer
Prostate Cancer
Published in: Cancer Immunology, Immunotherapy / Issue 4/2024
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-024-03640-6

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