NCT05917470终止1 期
A Phase 1/2 Study of ONCT-534 in Subjects With Metastatic Castration-Resistant Prostate Cancer
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 59
- 试验地点
- 9
- 主要终点
- Dose Limiting Toxicities Through Study Day 28
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Dose Level 1: 40mg QD
Experimental
40mg of single agent ONCT-534 to be administered daily in oral tablets
干预措施: ONCT-534 (Drug)
Dose Level 2: 80mg QD
Experimental
80mg of single agent ONCT-534 to be administered daily in oral tablets
干预措施: ONCT-534 (Drug)
Dose Level 3: 160mg QD
Experimental
160mg of single agent ONCT-534 to be administered daily in oral tablets
干预措施: ONCT-534 (Drug)
Dose Level 4: 300mg QD
Experimental
300mg of single agent ONCT-534 to be administered daily in oral tablets
干预措施: ONCT-534 (Drug)
Dose Level 5: 600mg QD
Experimental
600mg of single agent ONCT-534 to be administered daily in oral tablets
干预措施: ONCT-534 (Drug)
Dose Level 6: 1200 mg QD
Experimental
1200mg of single agent ONCT-534 to be administered daily in oral tablets
干预措施: ONCT-534 (Drug)
BID Dose Level 1: 160 mg BID
Experimental
600mg of single agent ONCT-534 to be administered daily in oral tablets
干预措施: ONCT-534 (Drug)
BID Dose Level 2: 300 mg BID
Experimental
300mg of single agent ONCT-534 to be administered twice daily in oral tablets
干预措施: ONCT-534 (Drug)
结局指标
主要结局
Dose Limiting Toxicities Through Study Day 28
时间窗: Number of Participants with Dose Limiting Toxicities Through Study Day 28
Incidence of DLTs through Study Day 28
次要结局
- Reduction of Prostate-Specific Antigen (PSA) by More Than 50%(Up to 51 Weeks)
研究者
研究点 (9)
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相关资讯
ONCT-534 Shows Promise in Metastatic Castration-Resistant Prostate Cancer- Oncternal Therapeutics' ONCT-534 demonstrates potential in treating relapsed or refractory metastatic castration-resistant prostate cancer (mCRPC).
- Twice-daily dosing of ONCT-534 was well-tolerated, with one patient experiencing a significant PSA reduction and target lesion decrease at a higher dose.
- Circulating tumor cell (CTC) analysis revealed promising effects on androgen receptor (AR)-regulated genes and AR nuclear translocation in some patients.
- The company is exploring strategic alternatives to further develop ONCT-534, including potential use in earlier lines of therapy for advanced prostate cancer.last yearOncternal Therapeutics Halts Clinical Trials, Initiates Layoffs After Disappointing Results- Oncternal Therapeutics discontinues clinical trials for ONCT-534 in prostate cancer and ONCT-808 in B-cell lymphoma due to lackluster Phase I results and a patient death.
- The company's stock price plummeted by 60% following the announcement, leading to a restructuring that includes laying off 37% of its workforce.
- This decision follows previous trial terminations of zilovertamab, a tyrosine kinase inhibitor, in April 2023, compounding financial pressures.
- Oncternal plans to explore alternative options for its programs while focusing on cost reduction measures and workforce optimization.2 years ago