Phase II two-arm study of AZD4635 in combination with durvalumab and in combination with cabazitaxel and durvalumab in patients with mCRPC

Recruitment & Eligibility

Status: ot Recruiting

Sex: Male

Target Recruitment: 80

Inclusion Criteria

1 Participant must be 18 years of age inclusive at the time of signing the informed consent.
2 Histologically confirmed adenocarcinoma of the prostate.
3 Known castrate-resistant disease.
4 Evidence of disease progression =6 months.
5 Body weight >30 kg at screening.
6 Willingness to adhere to the study treatment-specific contraception requirements.
7 Adequate bone marrow reserve and organ function.
8 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
9 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
10 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
11 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 16
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 64

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, 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.
7 History of allogeneic organ transplantation.-
8 Active or prior documented autoimmune or inflammatory disorders
9 History of active primary immunodeficiency.
10 Active infection including tuberculosis
11 Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention.
12 Ongoing treatment with warfarin (Coumadin).
13 Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study intervention.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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