A Study of AZD4635 With Durvalumab and With Cabazitaxel and Durvalumab in Patients With mCRPC.
Condition: Progressive Metastatic Castrate-Resistant Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: AZD4635; Durvalumab; Cabazitaxel
Intervention description: Subjects will receive AZD4635 orally daily; Subjects will receive intravenous durvalumab every 4 weeks for Arm A and every 3 weeks for Arm B.; Subjects will receive intravenous cabazitaxel every 3 weeks
Intervention MeSH terms: Durvalumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: Male
Minimum age: 18 Years
Maximum age: 150 Years
Healthy volunteers: No
Keywords: Prostate Cancer

Summary:

      This is a Phase II, international, open-label, two-arm, non-randomised study of AZD4635 in
      participants with metastatic castration-resistant prostate cancer (mCRPC).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically confirmed adenocarcinoma of the prostate.

          2. Known castrate-resistant disease.

          3. Evidence of disease progression ≤6 months.

          4. Body weight >30 kg at screening.

          5. Willingness to adhere to the study treatment-specific contraception requirements.

          6. Adequate bone marrow reserve and organ function.

          7. Adequate organ function for Arm A as demonstrated by all of the following laboratory
             values:

               -  Alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN) if no
                  demonstrable liver metastases or ≤5 × ULN in the presence of liver metastases.

               -  Aspartate aminotransferase (AST) ≤2.5 × ULN if no demonstrable liver metastases
                  or ≤5 × ULN in the presence of liver metastases

               -  Total bilirubin (TBL) ≤1.5 × ULN

               -  TBL ≤2.0 × ULN in the case of known Gilbert syndrome with normal direct bilirubin

          8. Participants in Arm A must have received the following prior therapy:

               -  Maximum of 3 lines of therapy in the mCRPC setting

               -  Prior therapy with one or more NHAs (eg, abiraterone acetate, enzalutamide,
                  apalutamide, darolutamide) in either hormone-sensitive or hormone-refractory
                  settings

               -  Prior therapy with one or more lines of taxanes (eg, docetaxel and/or
                  cabazitaxel)

               -  Alternatively, must be taxane-ineligible

               -  Prior therapy can be in either the hormone-sensitive or the hormone-refractory
                  setting

          9. Adequate organ function for Arm B as demonstrated by all of the following laboratory
             values:

               -  AST and/or ALT ≤1.5 × ULN

               -  TBL ≤ ULN

               -  TBL ≤2.0 × ULN in the case of known Gilbert syndrome with normal direct bilirubin

         10. Participants in Arm B must have received the following prior therapy:

               -  Prior docetaxel (taxane) in either hormone-sensitive or hormone-refractory
                  settings

               -  Received no prior cytotoxic chemotherapy other than docetaxel for prostate cancer
                  except for estramustine and except adjuvant/neo-adjuvant treatment completed >3
                  years ago.

               -  Prior therapy with only one NHAs (eg, abiraterone acetate or enzalutamide; prior
                  apalutamide is not permitted) for treatment of mCRPC in either hormone-sensitive
                  or hormone-refractory settings.

               -  Be suitable to receive concomitant Granulocyte-colony stimulating factor during
                  all cycles of cabazitaxel.

               -  Participants who meet inclusion criteria for Arm B will be allocated
                  preferentially to that arm until recruitment to that arm is completed.

        Exclusion Criteria:

          1. Active brain metastases or leptomeningeal metastases.

          2. There must be no requirement for immunosuppressive doses of systemic corticosteroids
             for at least 2 weeks prior to study enrollment.

          3. History of pneumonitis requiring corticosteroids, second malignancy that is
             progressing and/or received active treatment ≤3 years before the first dose of study
             intervention, and hypersensitivity to polysorbate-80 if allocated to cabazitaxel.

          4. As judged by the Investigator, any evidence of severe or uncontrolled systemic
             diseases.

          5. Creatinine clearance <40 mL/min (calculated by Cockcroft-Gault equation).

          6. Prior exposure to immune-mediated therapy including.

          7. Ongoing treatment with warfarin (Coumadin).

          8. Major surgery (excluding placement of vascular access) within 4 weeks of the first
             dose of study intervention.