A Phase 1 First-in-Human, Open-Label, Multicenter Study of OP-3136 in Adult Participants With Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 180
- 试验地点
- 8
- 主要终点
- Number of participants with dose-limiting toxicities in the Dose Escalation Arms
研究概览
简要总结
This is a first-in-human, open-label, multicenter phase 1 study to evaluate safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of OP-3136, a lysine acetyltransferases 6A and 6B (KAT6A/B) inhibitor, as monotherapy and in combination with other anticancer agents in participants with advanced solid tumors.
This study consists of 2 parts: a dose escalation part (Part 1) and dose expansion part (Part 2).
详细描述
Part 1A (Dose Escalation for OP-3136 Monotherapy): This part of the study will evaluate the safety, tolerability, and PK in a range of doses of OP-3136, a lysine acetyltransferases 6A and 6B (KAT6A/B) inhibitor, administered orally once daily to participants with ER+ HER2- advanced or metastatic breast cancer (mBC), advanced or metastatic castration resistant prostate cancer (mCRPC), or advanced or metastatic non-small cell lung cancer (mNSCLC), and determine the maximum tolerated dose (MTD) and the recommended dose/regimen for expansion (RDE).
Part 1B (Dose Escalation for OP-3136 in Combination with Fulvestrant): This part of the study will evaluate the safety and PK of OP-3136 administered in combination with fulvestrant in participants with ER+ HER2- mBC, and determine MTD and RDE for this combination.
Part 1C (Dose Escalation for OP-3136 in Combination with Palazestrant): This part of the study will evaluate the safety and PK of OP-3136 administered in combination with palazestrant in participants with ER+ HER2- mBC, and determine MTD and RDE for this combination.
Part 2A (Dose Expansion for OP-3136 Monotherapy): This part will evaluate two expansion cohorts at the monotherapy RDE from part 1 in participants with ER+ HER2- mBC and participants with mCRPC.
Part 2B (Dose Expansion for OP-3136 in Combination with Fulvestrant OR Palazestrant): This part will evaluate the RDEs for OP-3136 in combination with fulvestrant from Part 1B OR the RDEs of OP-3136 in combination with palazestrant in an expansion cohort in participants with ER+ HER2- mBC.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with advanced or metastatic ER+HER2- breast cancer, mCRPC, or NSCLC (Part 1) or advanced or metastatic ER+HER2- BC or mCRPC (Part 2).
- •Part 1A (Dose escalation for OP-3136 monotherapy): Participants must have a tumor that is unresectable or metastatic and for which life prolonging measures do not exist or available therapies are intolerable or no longer effective.
- •Part 1B (Dose escalation for OP-3136 in combination with fulvestrant): Participants with advanced or metastatic ER+ HER2- breast cancer that have progressed on or after at least 1 prior line of treatment that included endocrine therapy and CDK 4/6 inhibitor in advanced or metastatic setting and must have received no more than 2 prior lines of endocrine therapy (one of which must be in combination with CDK4/6 inhibitor) and no more than 1 prior line of chemotherapy or an antibody-drug conjugate in the advanced or metastatic setting.
- •Part 1C (Dose escalation for OP-3136 in combination with palazestrant): Participants with advanced or metastatic ER+ HER2- breast cancer that have progressed on or after at least 1 prior line of treatment that included endocrine therapy and CDK 4/6 inhibitor in advanced or metastatic setting and must have received no more than 2 prior lines of endocrine therapy (one of which must be in combination with CDK4/6 inhibitor) and no more than 1 prior line of chemotherapy or an antibody-drug conjugate in the advanced or metastatic setting.
- •Part 2A (Dose Expansion in ER+ HER2- mBC for OP-3136 monotherapy): Participants must have received up to 3 prior lines of endocrine therapy (one of which must be in combination with CDK4/6 inhibitor) and up to 1 prior line of chemotherapy or an antibody-drug conjugate.
- •Part 2A (Dose Expansion in mCRPC for OP-3136 monotherapy): Participants must have received up to 4 lines of prior systemic therapy for prostate cancer. Prior therapy must include treatment with an androgen receptor pathway inhibitor(s).
- •Part 2B (Dose Expansion in ER+ HER2- mBC for OP-3136 in combination with fulvestrant OR Dose Expansion in ER+ HER2- mBC for OP-3136 in combination with palazestrant): Participants must have progressed on or after at least 1 prior line of treatment that included endocrine therapy and CDK 4/6 inhibitor in advanced or metastatic setting. Participants must have received no more than 2 prior lines of endocrine therapy in the advanced or metastatic setting and no more than 1 prior line of chemotherapy or an antibody-drug conjugate in the advanced or metastatic setting.
排除标准
- •Prior therapy with KAT6A/B inhibitor in any treatment setting.
- •Participants with advanced/metastatic, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term.
- •Known active or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, leptomeningeal disease, or a spinal cord compression that require CNS-specific treatment, or participants who did not demonstrate clinical and radiologic stability during the last 2 months prior to the first dose of study treatment or require or are currently on steroid therapy for CNS metastases.
- •History of cerebral vascular disease, including transient ischemic attack, within 6 months prior to the first dose of study treatment.
- •History of or ongoing impaired cardiac function or clinically significant cardiac disease within 6 months prior to the first dose of study treatment.
- •Note: Additional inclusion/exclusion criteria may apply.
研究组 & 干预措施
Part 1A Dose Escalation monotherapy
干预措施: OP-3136 (Drug)
Part 1B Dose Escalation in combination with fulvestrant
干预措施: OP-3136 (Drug)
Part 1B Dose Escalation in combination with fulvestrant
干预措施: Fulvestrant (Drug)
Part 1C Dose Escalation in combination with palazestrant
干预措施: OP-3136 (Drug)
Part 1C Dose Escalation in combination with palazestrant
干预措施: Palazestrant (Drug)
Part 2A Dose Expansion monotherapy - mBC
干预措施: OP-3136 (Drug)
Part 2A Dose Expansion monotherapy - mCRPC
干预措施: OP-3136 (Drug)
Part 2B Dose Expansion in combination with fulvestrant OR palazestrant-mBC @ RDE 1
干预措施: OP-3136 (Drug)
Part 2B Dose Expansion in combination with fulvestrant OR palazestrant-mBC @ RDE 1
干预措施: Fulvestrant (Drug)
Part 2B Dose Expansion in combination with fulvestrant OR palazestrant-mBC @ RDE 1
干预措施: Palazestrant (Drug)
Part 2B Dose Expansion in combination with fulvestrant OR palazestrant-mBC @ RDE 2
干预措施: OP-3136 (Drug)
Part 2B Dose Expansion in combination with fulvestrant OR palazestrant-mBC @ RDE 2
干预措施: Fulvestrant (Drug)
Part 2B Dose Expansion in combination with fulvestrant OR palazestrant-mBC @ RDE 2
干预措施: Palazestrant (Drug)
结局指标
主要结局
Number of participants with dose-limiting toxicities in the Dose Escalation Arms
时间窗: Up to 28 days
Incidence of adverse events and laboratory abnormalities
时间窗: Up to 26 months
次要结局
- Duration of Response (DOR)(Up to 26 months)
- Maximum observed concentration (Cmax)(Up to 26 months)
- Overall Response Rate (ORR)(Up to 26 months)
- Time to maximum concentration (Tmax)(Up to 26 months)
- Area under the curve from time zero to 24 hours (AUC0-24)(Up to 26 months)
- Clinical Benefit Rate (CBR)(Up to 26 months)