A Study of AZD4635 With Durvalumab and With Cabazitaxel and Durvalumab in Patients With mCRPC.

• Status: Active, not recruiting
• Trial end date: 2022-11-01
• Target enrollment: 0
• Participant gender: Male

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AstraZeneca
• Collaborator: Parexel
• Treatments: Durvalumab

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.