SARUPARIB for Metastatic castration-sensitive prostate cancer

Inclusion criteria

• {"criterion_text":"- Male ≥ 18 years of age.\n- Participants must use a condom from signing ICF, during study intervention, and for 6 months after the last dose of study drug, with all sexual partners.\n- Histologically documented prostate adenocarcinoma which is de novo or recurrent and castration-sensitive. Participants with pathologic features of small cell, neuroendocrine, sarcomatoid, spindle cell, or signet cell histology are not eligible.\n- Metastatic disease as documented by the investigator prior to randomisation, with clear evidence of ≥ 1 bone lesion and/or ≥ 1 soft tissue lesion that is suitable for repeated assessment with CT and/or MRI.\n- Participant is receiving ADT with a GnRH analogue or has undergone bilateral orchiectomy starting ≥ 14 days and < 4 months prior to randomisation.\n- ECOG performance status of 0 or 1 with no deterioration over the 2 weeks prior to randomisation.\n- Provision of FFPE tumour tissue sample and blood sample (for ctDNA).\n- Confirmed HRRm status by central tumour tissue and/or ctDNA test is required to determine cohort eligibility.\n- Adequate organ and bone marrow function as described in study protocol.\n- Participants must not father children or donate sperm from signing ICF, during the study intervention and for 6 months after the last dose of study intervention."}

Exclusion criteria

• {"criterion_text":"- Participants with a history of MDS/AML or with features suggestive of MDS/AML (as determined by prior diagnostic investigation). In case there is no clinical MDS/AML suspicion, no specific screening for MDS/AML (by BM/bone biopsy) is required.\n- Cardiac criteria, including history of arrythmia and cardiovascular disease.\n- Any prior anticancer pharmacotherapy or surgery for metastatic prostate cancer, with the following exceptions: a) ≤ 4 months ADT for metastatic disease (per inclusion criterion 4). b) Radiation therapy (for example radiation therapy to the prostate for participants with low volume metastatic disease or palliative radiation therapy to treat symptoms resulting from metastatic disease). Radiation therapy needs to have been completed > 4 weeks prior to randomisation for wide field radiation therapy and > 2 weeks for limited field radiation therapy. Participants should have fully recovered from any clinically significant adverse events. c) Surgical therapy to treat symptoms from metastatic disease if it was completed at least 4 weeks prior to first day of dosing and participant fully recovered from any clinically significant AEs.\n- Patients in whom the standard of care is judged by the investigator to be docetaxelin combination with darolutamide.\n- Prior treatment within 14 days with blood product support or growth factor support.\n- Participants who are unevaluable for both bone and soft tissue progression.\n- Participants with any known predisposition to bleeding.\n- Any history of persisting (> 2 weeks) severe cytopenia.\n- Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD5305 and/or the assigned NHA.\n- History of another primary malignancy, with the following exceptions: a) Adequately resected non-melanoma skin cancer. b) Curatively treated in situ disease. c) Malignancy treated with curative intent ≥ 3 years before the first dose of study intervention, and with no known active disease during the intervening time period.\n- Persistent toxicities (CTCAE Grade ≥ 2) caused by previous anticancer therapy.\n- Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention."}

Primary endpoints

• {"endpoint_text":"- Radiographic progression-free survival, defined as the time from randomisation to radiographic progression, as assessed by the investigator per RECIST 1.1 (soft tissue) and/or PCWG3 criteria (bone) or death due to any cause.","definition_or_measurement_approach":"Defined as time from randomisation to radiographic progression assessed by investigator per RECIST 1.1 (soft tissue) and/or PCWG3 (bone) or death from any cause."}

Secondary endpoints

• {"endpoint_text":"- Overall Survival, defined as the time from the date of randomisation until death due to any cause.","definition_or_measurement_approach":"Defined as time from randomisation until death due to any cause."}
• {"endpoint_text":"- Time to Second Progression or Death (PFS2), defined as the time from randomisation to the earliest progression after initiation of first subsequent treatment following the initial investigator-assessed progression or death.","definition_or_measurement_approach":"Defined as time from randomisation to earliest progression after starting first subsequent treatment following initial investigator-assessed progression, or death."}
• {"endpoint_text":"- Time to First Subsequent Therapy or Death (TFST), defined as the time from randomisation to the start date of the first subsequent anticancer therapy after discontinuation of randomised treatment, or death due to any cause.","definition_or_measurement_approach":"Defined as time from randomisation to start date of first subsequent anticancer therapy after discontinuation of randomised treatment, or death."}
• {"endpoint_text":"- Symptomatic Skeletal Event-free Survival.","definition_or_measurement_approach":"Symptomatic skeletal event-free survival (definition not further detailed in Part I data; endpoint recorded as SE-free survival)."}
• {"endpoint_text":"- Time to Castration-Resistance (TTCR), defined as the time from randomisation to the first castration-resistant event.","definition_or_measurement_approach":"Defined as time from randomisation to first castration-resistant event."}
• {"endpoint_text":"- Clinical Outcome Assessments, including TTPP, TTDUS, TTDF, TTDPF, and HRQoL.","definition_or_measurement_approach":"Clinical outcome assessments include measures such as time to progression of pain (TTPP), time to deterioration of urinary symptoms (TTDUS), time to fatigue deterioration (TTDF), time to deterioration of physical function (TTDPF), and health-related quality of life (HRQoL) assessments as specified in study documents."}

Primary sponsor

Full Name

AstraZeneca AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden