Progressive Metastatic Castrate-Resistant Prostate Cancer MedDRA version: 21.1 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Code: AZD4635
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Not applicable
CAS Number: 1321514-06-0
Current Sponsor code: AZD4635
Other descriptive name: SSP002388X, SPD559
Concentra
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
Male
Inclusion criteria
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 - Disease must be metastatic and inoperable and for which there is no curative intervention available. Participants may have bone-only disease. - Participants presenting with treatment-emergent neuroendocrine differentiation, but not primary small-cell features, are eligible. 3 Known castrate-resistant disease, defined as: - Testosterone level in the castration range (levels 30 kg at screening. 7 Willingness to adhere to the study treatment-specific contraception requirements: Participants must be surgically sterile or using an acceptable method of contraception (defined as barrier methods in conjunction with spermicides) for the duration of the study (from the time they sign ICF) and for 3 months after the last dose of AZD4635 and/or durvalumab and/or cabazitaxel to prevent pregnancy in a female partner. Participants must not donate or bank sperm for 24 weeks after treatment. 8 Adequate bone marrow reserve and organ function as demonstrated by all of the following laboratory values: - Absolute neutrophil count (ANC) =1.5 × 10^9/L - Platelet count =100 × 10^9/L - Haemoglobin =9.0 g/dL - Creatinine =1.5 × ULN concurrent with creatinine clearance >50 mL/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is >1.5 × ULN. Additional Inclusion Criteria Specific for Arm A 9 Adequate organ function for Arm A as demonstrated by all of the following laboratory values: - Alanine aminotransferase (ALT) =2.5 × the 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 10 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-refract
Exclusion criteria
Exclusion criteria: 1 Active brain metastases or leptomeningeal metastases. Participants with brain metastases are eligible if treated and there is no evidence of progression for at least 8 weeks after treatment is completed and within 28 days prior to the first dose of study intervention. 2 There must be no requirement for immunosuppressive doses of systemic corticosteroids (>10 mg/day prednisone/equivalent) for at least 2 weeks prior to study enrollment. 3 Participant with a history of pneumonitis requiring corticosteroids. 4 History of a second malignancy that is progressing and/or received active treatment =3 years before the first dose of study intervention. 5 As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or active infection including hepatitis B, hepatitis C, and human immunodeficiency virus. Screening for chronic conditions is not required. 6 Creatinine clearance <50 mL/min (calculated by Cockcroft-Gault equation). 7 Prior exposure to immune-mediated therapy including, but not limited to anti-CTLA-4, anti-PD-1, anti-PD-L1 and anti-PD-L2 antibodies, excluding therapeutic anti-cancer vaccines. Additional Exclusion Criteria Specific for Arm B: Medical Conditions 8 Participant with active grade =2 peripheral neuropathy 9 Participant with active grade =2 stomatitis 10 Any small-molecule, biologic, or hormonal agent from a previous treatment regimen or clinical study within 21 days or 5 half-lives (whichever is shorter) prior to the first dose of study intervention. At least 7 days must have elapsed between the last dose of such agent and the first dose of study intervention. Exception: androgen-deprivation therapy is permitted. 11 History of hypersensitivity to polysorbate-80 if allocated to cabazitaxel. 12 Nitrosourea or mitomycin C within 6 weeks of the first dose of study intervention. 13 Prescription or non-prescription drugs or other products known to be sensitive BCRP or OAT1 substrates or to be strong inhibitors/inducers of CYP1A2, which cannot be discontinued 2 weeks prior to Day 1 of dosing and withheld throughout the study, until 2 weeks after the last dose of study intervention. 14 Exclusion Criteria for Arm B: Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (CYP3A4/5) are excluded (a 2-week washout period is required for participants already on these treatments). 15 Herbal preparations/medications are not allowed throughout the study. These herbal medications include but are not limited to St. John’s wort, kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone, yohimbe, saw palmetto, and ginseng. Participants should stop using these herbal medications 7 days prior to the first dose of study intervention. Exceptions may be agreed, but the circumstances must be reviewed by the Medical Monitor/AZ Study Physician in advance. 16 Ongoing treatment with warfarin (Coumadin). 17 Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention. 18 Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study intervention. 19 Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study intervention. 20 AZD4635 in the present study (i.e., dosing with AZD4635 previously initiated in a different arm in this study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy (as assessed by radiographic progression free survival [rPFS]) of AZD4635 plus durvalumab and separately of AZD4635 plus durvalumab plus cabazitaxel in participants with mCRPC.;Secondary Objective: *To determine the efficacy of AZD4635 plus durvalumab and separately of AZD4635 plus durvalumab plus cabazitaxel by assessment of overall survival (OS), objective response rate (ORR), duration of response (DoR), prostate-specific antigen (PSA) response in participants with mCRPC. *Investigate the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel. *To determine the efficacy of AZD4635 plus durvalumab and AZD4635 plus durvalumab plus cabazitaxel in participants with mCRPC, by adenosine (ADO) gene expression in high and low subgroups in each arm separately. *To determine the efficacy of AZD4635 plus durvalumab and AZD4635 plus durvalumab plus cabazitaxel in participants with mCRPC, by adenosine deaminase (ADA) gene expression in high and low subgroups in each arm separately. *To explore the effects of AZD4635 on pain and other prostate cancer-related symptoms.;Primary end point(s): rPFS, defined as the time from first dose to radiographic progression as assessed by the Investigator per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) (soft tissue) and Prostate Cancer Working Group 3 criteria (PCWG3) (bone) or death from any cause, whichever occurs first.;Timepoint(s) of evaluation of this end point: •Arm A: RECIST and PCWG3 measurements will be made every 8 weeks (±1 week) for the first 24 weeks relative to the start of study treatment (Cycle 1, Day 1) and every 12 weeks (±1 week) thereafter until RECIST 1.1 defined disease progression or cessation of study treatment (if treating beyond disease progression).” •Arm B: RECIST and PCWG3 measurements will be made every 9 weeks (±1 week) for the first 27 weeks relative to the start of study treatment (Cycle 1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Overall survival (also within the gene expression subgroups) - Objective response rate (also within the gene expression subgroups) - Duration of response (also within the gene expression subgroups) - Prostate-specific antigen response (also within the gene expression subgroups) - AZD4635, durvalumab and cabazitaxel plasma concentration and derived PK parameters. - Radiographic progression free survival within the gene expression subgroups - Change from baseline in worst pain, general pain and pain interference in the daily activities scales of the BPI-SF and in the worst bone pain item. - Time to pain progression based on BPI-SF Item 3 “worse pain in 24-hours”. - Change from baseline in the FAPSI-8, as derived from 8 items within the FACT-P and the PCS, as derived from the 12 items in the prostrate-specific module of the FACT-P.;Timepoint(s) of evaluation of this end point: •RECIST and PCWG3 measurements will be made every 8 ± 1 weeks (Arm A) or 9 ±1 weeks (Arm B) for the first 24 weeks (Arm A) or 27 weeks (Arm B) relative to the start of study treatment and every 12 ±1 weeks thereafter until RECIST 1.1 defined disease progression or cessation of study treatment •OS: will be determined every 3 months from disease progression until data cut-off or death •PK: will be measured at limited time points during treatment and up to follow up •PSA assessment at baseline and at the start of each new treatment cycle (every 4 weeks for arm A and every 3 weeks for first 10 cycles and then every 4 weeks arm B), at end of treatment, and at progression • BPI-SF and FACT-P assessments will be measured at limited time points during treatment and up to follow up | — |
Countries
Belgium, Denmark, France, Germany, Italy, Korea, Republic of, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed