A phase 2 study of AZD4635 in combination with durvalumab or oleclumab in patients with metastatic castration-resistant prostate cancer.
A2AR antagonist
AZD4635
Adenosine
Durvalumab
Metastatic castration-resistant prostate cancer
Oleclumab
Journal
Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
Titre abrégé: Cancer Immunol Immunother
Pays: Germany
ID NLM: 8605732
Informations de publication
Date de publication:
02 Mar 2024
02 Mar 2024
Historique:
received:
22
09
2023
accepted:
22
01
2024
medline:
2
3
2024
pubmed:
2
3
2024
entrez:
2
3
2024
Statut:
epublish
Résumé
Inhibition of the adenosine 2A receptor (A 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. 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. In this heavily pretreated population, AZD4635 with durvalumab or oleclumab demonstrated minimal antitumor activity with a manageable safety profile. gov identifier: NCT04089553.
Sections du résumé
BACKGROUND
BACKGROUND
Inhibition of the adenosine 2A receptor (A
METHODS
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
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
CONCLUSIONS
In this heavily pretreated population, AZD4635 with durvalumab or oleclumab demonstrated minimal antitumor activity with a manageable safety profile.
CLINICAL TRIAL
BACKGROUND
gov identifier: NCT04089553.
Identifiants
pubmed: 38430405
doi: 10.1007/s00262-024-03640-6
pii: 10.1007/s00262-024-03640-6
doi:
Banques de données
ClinicalTrials.gov
['NCT04089553']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
72Informations de copyright
© 2024. The Author(s).
Références
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