A Clinical Study of ONCT-534 in Subjects With Metastatic Castration-resistant Prostate Cancer.

A Phase 1/2 Study of ONCT-534 in Subjects With Metastatic Castration-Resistant Prostate Cancer

A first-in-human clinical trial to test the investigational treatment ONCT-534 in participants with metastatic castration-resistant prostate cancer. The main questions it aims to answer are:

• What are the most tolerable doses of ONCT-534? (Phase 1)
• Does ONCT-534 have anti-tumor activity at tolerable doses? (Phase 2)

This is a dose escalation and expansion study where participants will receive daily oral doses of ONCT-534.

This is a Phase 1/2 multi-center study to investigate the safety, tolerability, and anti-tumor acitivity of ONCT-534 in patients with relapsed or refractory metastatic castration-resistant prostate cancer. The study consists of 2 phases: a Phase 1 Dose Escalation and a Phase 2 Dose Expansion.

• During the dose escalation in Phase 1 a group of participants will be assigned a certain dose level. Once the dose level is considered safe, the next group will be assigned a higher dose level. The dose level may be raised or lowered depending on any safety events that occur throughout Phase 1. There will be approximately 27 participants enrolled in Phase 1. At the end of Phase 1, two dose levels will be chosen to be tested in Phase 2.
• During Phase 2, participants will be randomly assigned to 1 of the 2 dose levels chose in Phase 1. Approximately 16 participants will be enrolled in each of the 2 dose level groups, for a total of 32 participants.

Inclusion Criteria:

• Subject is ≥18 years of age
• Subject has histologically documented metastatic adenocarcinoma of the prostate confirmed by biopsy without neuroendocrine differentiation or small cell features.
• Subjects has a history of metastatic CRPC.
• Subject has R/R disease following treatment with at least one next-generation AR-signaling inhibitor.
• Subject has at least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria or evaluable bony disease. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.
• Subject has an Eastern Cooperative Oncology Group performance status of 0,1 or 2, and life expectancy of ≥ 6 months.
• Subject agrees to take or continue luteinizing hormone-releasing hormone agonist or antagonist therapy or has undergone bilateral orchiectomy.
• At least 2 weeks or five half-lives have elapsed, whichever is earliest, since last systemic therapy, including taxanes or other chemotherapy. At least one month has elapsed since systemic therapy with radionuclide pharmaceutical agents
• Subject has evidence of disease progression on or after their most recent systemic treatment
• Subject has a PSA level ≥ 10 ng/mL, or ≥ 2 ng/mL and ≥ 50% increase from nadir on prior therapy, whichever is lowest.
• Subject has serum testosterone < 50 ng/dL.
• Subject has adequate renal, hepatic, and pulmonary function
• Subject is committed to practice true abstinence, or use a highly effective method of contraception with any female partner of childbearing potential unless documented to be surgically sterile (i.e., vasectomy or bilateral orchiectomy) and to not make semen donations during the study and for 3 months after the last dose of study drug.

Exclusion Criteria:

• Subject has small cell prostate cancer or neuroendocrine disease histology, including mixed histology.
• Subject has metastases to the brain or central nervous system
• Subject is receiving concurrent anti-cancer therapy (including chemotherapy, antibody therapy, immunotherapy, cellular therapy, or other experimental therapies) except for ongoing androgen inhibiting therapy such as luteinizing hormone-releasing hormone (LHRH) agonists. Supportive non-cancer directed therapies such as bisphosphonates or denosumab are allowed.
• Subjects taking a strong inhibitor of CYP3A4 or a substrate of CYP2C9 or CYP2C19
• Subject had major surgery within 30 days prior to start of study drug.
• Subject has current, untreated pathologic long-bone fractures(s), or risk of imminent pathologic fracture(s).
• Subject has current or imminent spinal cord compression.
• Subject has an active seizure disorder or a history of seizure disorder(s).
• Subject has evidence of active human immunodeficiency virus infection, hepatitis B virus (HBV), or hepatitis C virus (HCV)
• Subject has any other serious illness or medical condition that would interfere with study participation
• Subject has abnormal electrocardiograms (ECGs) that are clinically significant, including average QTcF > 450 ms, or a history of Torsade de Pointes.
• Subject has any infection requiring parenteral antibiotic therapy or causing fever (temperature >100.5°F or 38.1°C) within 1 week prior to first dose.
• Clinically significant other malignancy with the potential to confound study assessments, with the exception of e.g., treated cutaneous squamous cell and basal carcinomas, non-muscle invasive bladder cancer, Rai Stage 0 CLL, and adequately treated Stage 1 to 2 non-cutaneous malignancy in remission for 5 years.
• Subject is unable to comply with the protocol and/or not willing or not available for follow-up assessments
• Subject has any medical intervention or other condition which, in the opinion of the Investigator, could compromise adherence with study requirements or otherwise compromise the study's objectives.