Study of AZD5305 when given in combination with New Hormonal Agents in Patients with Metastatic Prostate Cancer - PETRANHA

Exclusion Criteria

• For Part A mCRPC patients only:
• • Any previous treatment with a new hormonal agent (NHA), poly (adenosine diphosphateribose) polymerase inhibitor (PARPi), Lutetium prostate-specific membrane antigen (Lu-PSMA), platinum chemotherapy
• • Patients recruited to the PDc cohorts should not have received a prior use of new hormonal agents (NHA).
• For Part A and Part B mCSPC Patients:
• • Any previous treatment with a PARPi, platinum, NHA, Immuno-oncology (IO), radiopharmaceutical therapy, or prior treatment with docetaxel in mCSPC setting.
• • Concomitant use of medications or herbal supplements known to be:
• (a) Strong and moderate CYP3A4 inducers/inhibitors (applies for all arms)
• (b) For Arm 1 (enzalutamide) patients: Strong CYP2C8 inhibitors
• (c) For Arm 3 (darolutamide) patients: Strong P-glycoprotein inducers
• • Concomitant use of drugs that are known to prolong or shorten QT and have a known risk of Torsades de Pointes.
• • Treatment with any of the following:
• a) Any investigational agents or study interventions from a previous clinical study within 5 half lives or 3 weeks (whichever is longer) of the first dose of study treatment.
• b) Any other anticancer treatment within the following time periods prior to the first dose of study treatment: (i) Cytotoxic and non-cytotoxic treatment: 3 weeks or 5 half-lives (whichever is shorter). (ii) Biological products including immuno-oncology agents: 4 weeks before enrolment.
• c) Any live virus or bacterial vaccine within 28 days of the first dose of study treatment.
• • Any concurrent anticancer therapy or concurrent use of prohibited medications.
• • Major surgery within 4 weeks prior to the first dose of study treatment.
• • 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 treatment.
• • With the exception of alopecia, and peripheral neuropathy; any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of study enrolment.
• • Any history of persisting (> 2 weeks) severe pancytopenia.
• • Spinal cord compression, or brain metastases unless asymptomatic and treated and stable.
• • Any evidence of severe or uncontrolled systemic diseases, including, active bleeding diatheses, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).
• • Patients with any known predisposition to bleeding (eg, active peptic ulceration, recent [within 6 months] haemorrhagic stroke, proliferative diabetic retinopathy.
• • Any clinically significant cardiac disorders including QT prolongation, abnormal electrocardiogram (ECG).
• • Any clinically significant cardiovascular diseases including symptomatic heart failure, uncontrolled hypertension, acute coronary syndrome, cardiomyopathy, valvular heart disease, atrial fibrillation, stroke.
• • Patients with history of myelodysplastic syndrome (MDS)/ acute myeloid leukaemia (AML).
• • Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection.
• • Known allergy or hypersensitivity to investigational product(s) or any of the excipients of the investigational product(s).
• • Any condition that would interfere with evaluation of the study treatment or interpretation of patient safety or study results.
• • Uncontrolled intercurrent illness within the last 12 months, including but not limited to, active interstitial lung disease, serious chronic gastrointestinal (GI) conditions associated with diarrhoea, or psychiatric illness/social situations
• • History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study treatment and of low potential risk for recurrence.
• • Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• • Arm 1 (Enzalutamide) and Arm 4 (Apalutamide): History of seizure or any condition that may predispose to seizure (eg, prior cortical stroke, significant brain trauma).
• • Arm 2 (Abiraterone acetate) only: (i) Active infection or other medical condition that would contraindicate the use of systemic steroids (prednisone/prednisolone). (ii) Low serum potassium (< 3.5 mmol/L). (iii) History of uncontrolled pituitary or adrenal dysfunction.
• • Arm 4 (Apalutamide): (i) Moderate or severe skin conditions or diseases that could affect the skin (eg. scleroderma, lupus). (ii) Any skin or medical condition that in the Investigator's
• opinion could increase the risk of skin toxicity.