A phase II study (AARDVARC) of AZD4635 in combination with durvalumab and cabazitaxel in patients with progressive, metastatic, castration-resistant prostate cancer.
ESMO Open
; 9(6): 103446, 2024 Jun.
Article
in En
| MEDLINE
| ID: mdl-38838502
ABSTRACT
BACKGROUND:
This phase II nonrandomized study evaluated the efficacy and safety of AZD4635 in combination with durvalumab (Arm A) or durvalumab plus cabazitaxel (Arm B) in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel and ≥1 novel hormonal agent. PATIENTS ANDMETHODS:
The primary endpoint was radiographic progression-free survival (rPFS) per RECIST v1.1 (soft tissue) or the Prostate Cancer Clinical Trials Working Group 3 (bone). Secondary endpoints included safety, tolerability, overall survival, confirmed prostate-specific antigen (PSA50) response, pharmacokinetics, and objective response rate. Enrollment in Arm A was stopped following a sponsor decision unrelated to safety. The study was stopped based on the planned futility analysis due to low PSA50 response in Arm B.RESULTS:
In the final analysis (1 November 2021), 30 patients were treated (Arm A, n = 2; Arm B, n = 28). The median rPFS in Arm B was 5.8 months (95% confidence interval 4.2-not calculable). Median rPFS was 5.8 months versus 4.2 months for patients with high versus low blood-based adenosine signature. The most common treatment-related adverse events in Arm B were nausea (50.0%), diarrhea (46.4%), anemia and neutropenia (both 35.7%), asthenia (32.1%), and vomiting (28.6%). Overall, AZD4635 in combination with durvalumab or AZD4635 in combination with cabazitaxel and durvalumab showed limited efficacy in patients with mCRPC.CONCLUSIONS:
Although the safety profile of both combinations was consistent with known safety data of the individual agents, the results of this trial do not support further development of the combinations.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antineoplastic Combined Chemotherapy Protocols
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Prostatic Neoplasms, Castration-Resistant
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Antibodies, Monoclonal
Limits:
Aged
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Aged80
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Humans
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Male
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Middle aged
Language:
En
Journal:
ESMO Open
Year:
2024
Document type:
Article