An Open-label, Phase II Study of AZD4635 in Patients With Prostate Cancer
Condition: Prostate Cancer; Metastatic Castration-Resistant Prostate Cancer (mCRPC)
MeSH terms: Prostatic Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      This is an open-label Phase II modular study in participants with prostate cancer which will
      assess safety, efficacy, and tolerability of AZD4635 in combination with other therapeutic
      agents in different treatment arms (referred to as modules).

      Combinations to be studied include: 1) Module 1: AZD4635 plus durvalumab; 2) Module 2:
      AZD4635 plus oleclumab.
    

Detailed description: 
      This is an open-label Phase II modular study in participants with prostate cancer which will
      assess safety, efficacy, and tolerability of AZD4635 in combination with other therapeutic
      agents in different treatment arm (referred to as modules).

      Combinations to be studied include: 1) Module 1: AZD4635 plus durvalumab; 2) Module 2:
      AZD4635 plus oleclumab.

      All participants will be allocated into a module using an Interactive Web Response System
      (IWRS). Randomization will occur when patients meet eligibility criteria for two or more
      modules that are currently recruiting. If participants only meet the criteria for one
      currently recruiting module, they will be allocated to that module without randomization
      taking place.

      The primary objective of the clinical study is to evaluate the efficacy of each combination
      therapy by: 1) assessing the objective response rate (ORR) of participants with measurable
      disease (response will be determined by Response Evaluation Criteria in Solid Tumours [RECIST
      1.1]); 2) assessing the prostate-specific antiget (PSA) confirmed response rate of each
      combination therapy (PSA confirmed response rate is defined as the proportion of participants
      with a reduction in the PSA level of ≥50% measured from baseline to the lowest post-baseline
      PSA result measured twice, at least 3 weeks apart by the Prostate Cancer Working Group 3
      criteria [PCWG3]).

      The safety endpoints include assessment of adverse events and serious adverse events,
      physical examinations, vital signs, and collection of clinical chemistry/hematology
      parameters

      There will be approximately 30 PSA evaluable participants in each module, and approximately
      20 participants will have RECIST measurable disease at baseline in each module. If any of the
      required participants for PSA and/or ORR are not evaluable for PSA response or tumor
      response, respectively, they may be replaced at the sponsor's discretion.
    

Intervention name(s): AZD4635; Oleclumab; Durvalumab
Intervention type(s): Drug; Drug; Drug
Intervention description(s): In Module 1, participants will receive AZD4635 75 mg capsule orally QD for first 14 days and thereafter will continue to receive 75 mg orally QD Q4W.
In Module 2, participants will receive AZD4635 50 mg / 75 mg capsule orally QD Q2W of 28-day cycle for the first 4 doses and Q4W thereafter.
In both modules, participants will receive treatment until will derive clinical benefit as judged by the investigator or until confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurs first.; In Module 2, participants will receive oleclumab 1500 mg IV (solution for infusion after dilution, 50 mg/mL) Q2W of 28-day cycle for the first 4 doses and Q4W thereafter until will derive clinical benefit as judged by the investigator or until confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurs first.; In Module 1 after monotherapy of AZD4635, participants will receive durvalumab 1500 mg IV (solution for infusion after dilution, 50 mg/mL) Q4W until will derive clinical benefit as judged by the investigator or until confirmed disease progression, unacceptable toxicity, started alternative anticancer therapy, withdrawal of consent, or lost to-follow-up, whichever occurs first.
Other intervention name(s): MEDI9447; Imfinzi, MEDI4736
Intervention MeSH terms: Durvalumab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Prostate cancer; AZD4635; oleclumab; durvalumab; MEDI9447; Adenosine 2A Receptor Antagonist; A2AR