A Phase 1 Study of SY 5609, an Oral, Selective CDK7 Inhibitor, in Adult Patients With Select Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 105
- 试验地点
- 16
- 主要终点
- Groups 3 and 4 (Expansions): Progression Free Survival
研究概览
简要总结
The study consists of 2 parts. Part 1 is dose escalation and will first administer SY-5609 alone to participants with select advanced solid tumors and then in combination with fulvestrant to participants with HR positive, HER2-negative breast cancer. Part 2 is a dose expansion and will first administer SY-5609 in combination with gemcitabine and then SY-5609 in combination with gemcitabine and nab-paclitaxel in participants with pancreatic ductal adenocarcinoma (PDAC) .
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Age ≥ 18 years
- •Advanced Solid Tumors for which standard curative or palliative measures do not exist or are no longer effective (Group 1 only).
- •Postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer. Participants must have failed prior treatment with a cyclin-dependent kinase (CDK) 4/6 inhibitor in combination with hormonal therapy in a previous line of therapy (Group 2 only).
- •Participants with histologically or cytologically confirmed PDAC with measurable metastatic lesion(s) (Groups 3 and 4 only).
- •Participants must have at least 1 measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) v1.
- •All toxicities (except alopecia) from prior cancer treatments must have resolved to ≤ Grade 1 before enrollment.
- •For women of childbearing potential (WCBP): negative serum β human chorionic gonadotropin pregnancy test within 1 week before the first dose of SY 5609
- •Adequate organ and marrow function
- •Participants must be willing and able to comply with all aspects of the protocol
- •Participants must provide written informed consent before any study-specific screening procedures.
- •Albumin ≥ 3.0 grams/deciliters (g/dL) (Groups 3 and 4 only).
排除标准
- •Chemotherapy or limited field radiotherapy within 2 weeks, wide field radiotherapy within 4 weeks, or nitrosoureas or mitomycin C within 6 weeks before entering the study
- •Major surgery within 2 weeks before starting the study treatment, or not recovered to baseline status from the effects of surgery received > 2 weeks prior
- •Received any other investigational agents within 4 weeks before enrollment, or < 5 half-lives since completion of previous investigational therapy, whichever is shorter
- •Received previous noncytotoxic, US Food and Drug Administration-approved anticancer agent within previous 2 weeks, or < 5 half-lives since completion of previous therapy, whichever is shorter
- •Known brain metastases or carcinomatous meningitis
- •Immunocompromised participants with increased risk of opportunistic infections
- •Participants with known active or chronic hepatitis B or active hepatitis C infection. Participants with a history of hepatitis C virus (HCV) infection who have completed curative therapy for HCV at least 12 weeks before Screening and have a documented undetectable viral load at Screening are eligible for enrollment.
- •Baseline QT interval corrected (QTc) with Fridericia's method > 480 milliseconds
- •NOTE: criterion does not apply to participants with a right or left bundle branch block (QTc interval)
- •Female participants who are pregnant or breastfeeding
- •History of clinically significant cardiac disease or clinically relevant uncontrolled cardiac risk factors
- •Uncontrolled intercurrent illness.
- •Poorly controlled ascites requiring paracentesis within 1 month prior to entering the study. (Groups 3 and 4 only)
研究组 & 干预措施
Group 1: Single Agent Dose Escalation
Dose escalation phase to explore maximum tolerated dose of SY-5609 given as a single agent.
干预措施: SY-5609 (Drug)
Group 2: SY-5609 + Fulvestrant
Participants with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2) negative advanced or metastatic breast cancer (BC) that has progressed following prior treatment with a cyclin-dependent kinase (CDK)4/6 inhibitor in combination with hormonal therapy will receive SY-5609 in combination with fulvestrant.
干预措施: SY-5609 (Drug)
Group 2: SY-5609 + Fulvestrant
Participants with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2) negative advanced or metastatic breast cancer (BC) that has progressed following prior treatment with a cyclin-dependent kinase (CDK)4/6 inhibitor in combination with hormonal therapy will receive SY-5609 in combination with fulvestrant.
干预措施: Fulvestrant (Drug)
Group 3: SY-5609 + Gemcitabine
Participants with PDAC will receive SY-5609 in combination with gemcitabine in Safety Lead-in to identify a recommended combination dose for the expansion. The expansion part will assess the safety, tolerability, and preliminary clinical activity of SY-5609 in combination with gemcitabine at the recommended combination dose.
干预措施: SY-5609 (Drug)
Group 3: SY-5609 + Gemcitabine
Participants with PDAC will receive SY-5609 in combination with gemcitabine in Safety Lead-in to identify a recommended combination dose for the expansion. The expansion part will assess the safety, tolerability, and preliminary clinical activity of SY-5609 in combination with gemcitabine at the recommended combination dose.
干预措施: Gemcitabine (Drug)
Group 4: SY-5609 + Gemcitabine + Nab-paclitaxel
Participants with PDAC will receive SY-5609 in combination with gemcitabine plus nab-paclitaxel in Safety Lead-in to identify a recommended combination dose for the expansion. The expansion part will assess the safety, tolerability, and preliminary clinical activity of SY-5609 in combination with gemcitabine plus nab-paclitaxel at the recommended combination dose.
干预措施: SY-5609 (Drug)
Group 4: SY-5609 + Gemcitabine + Nab-paclitaxel
Participants with PDAC will receive SY-5609 in combination with gemcitabine plus nab-paclitaxel in Safety Lead-in to identify a recommended combination dose for the expansion. The expansion part will assess the safety, tolerability, and preliminary clinical activity of SY-5609 in combination with gemcitabine plus nab-paclitaxel at the recommended combination dose.
干预措施: Gemcitabine (Drug)
Group 4: SY-5609 + Gemcitabine + Nab-paclitaxel
Participants with PDAC will receive SY-5609 in combination with gemcitabine plus nab-paclitaxel in Safety Lead-in to identify a recommended combination dose for the expansion. The expansion part will assess the safety, tolerability, and preliminary clinical activity of SY-5609 in combination with gemcitabine plus nab-paclitaxel at the recommended combination dose.
干预措施: Nab-paclitaxel (Drug)
结局指标
主要结局
Groups 3 and 4 (Expansions): Progression Free Survival
时间窗: Up to 1 year
Groups 1 and 2: Number of Participants With Treatment Emergent Adverse Events
时间窗: From Baseline up to 30 days after last dose of study drug (up to 1 year)
Groups 3 and 4 (Safety Lead-ins): Number of Participants With Dose-Limiting Toxicity
时间窗: Up to 28 days after first administration
Groups 3 and 4 (Safety Lead-ins): Number of Participants With TEAEs
时间窗: From Baseline up to 30 days after last dose of study drug (up to 1 year)
Groups 1 and 2: Dose-Limiting Toxicity of SY-5609
时间窗: Up to 28 days after first administration
次要结局
- Groups 3 and 4 (Expansions): Complete Response Rate(Up to 1 year)
- Groups 3 and 4 (Expansions): Disease Control Rate(Up to 1 year)
- Groups 1 and 2: Area Under The Concentration Versus Time Curve of SY-6509(Predose, 0.5, 1, 2, 4, 6, 8 hours postdose on Day 1 and 4 or 15 of Cycle 1; 24 hours predose on Day 2 and 5 of Cycle 1; 24 hours predose on Day 1 of Cycle 2, 3 and 4 (Each Cycle=28 days))
- Groups 1 and 2: Apparent Volume of Distribution of SY-5609(Predose, 0.5, 1, 2, 4, 6, 8 hours postdose on Day 1 and 4 or 15 of Cycle 1; 24 hours predose on Day 2 and 5 of Cycle 1; 24 hours predose on Day 1 of Cycle 2, 3 and 4 (Each Cycle=28 days))
- Groups 1 and 2: Elimination Half-Life of SY-5609(Predose, 0.5, 1, 2, 4, 6, 8 hours postdose on Day 1 and 4 or 15 of Cycle 1; 24 hours predose on Day 2 and 5 of Cycle 1; 24 hours predose on Day 1 of Cycle 2, 3 and 4 (Each Cycle=28 days))
- Groups 1 and 2: Time of Maximum Plasma Concentration (Tmax) of SY-5609(Predose, 0.5, 1, 2, 4, 6, 8 hours postdose on Day 1 and 4 or 15 of Cycle 1; 24 hours predose on Day 2 and 5 of Cycle 1; 24 hours predose on Day 1 of Cycle 2, 3 and 4 (Each Cycle=28 days))
- Groups 3 and 4 (Safety Lead-ins): Objective Response Rate (ORR)(Up to 1 year)
- Groups 1 and 2: Apparent Clearance of SY-5609(Predose, 0.5, 1, 2, 4, 6, 8 hours postdose on Day 1 and 4 or 15 of Cycle 1; 24 hours predose on Day 2 and 5 of Cycle 1; 24 hours predose on Day 1 of Cycle 2, 3 and 4 (Each Cycle=28 days))
- Groups 1 and 2: Minimum or Trough Plasma Concentration (Cmin) of SY-5609(Predose, 0.5, 1, 2, 4, 6, 8 hours postdose on Day 1 and 4 or 15 of Cycle 1; 24 hours predose on Day 2 and 5 of Cycle 1; 24 hours predose on Day 1 of Cycle 2, 3 and 4 (Each Cycle=28 days))
- Groups 1 and 2: Maximum Plasma Concentration (Cmax) of SY-5609(Predose, 0.5, 1, 2, 4, 6, 8 hours postdose on Day 1 and 4 or 15 of Cycle 1; 24 hours predose on Day 2 and 5 of Cycle 1; 24 hours predose on Day 1 of Cycle 2, 3 and 4 (Each Cycle=28 days))
- Groups 3 and 4 (Safety Lead-ins): Duration of Response(Up to 1 year)
- Groups 3 and 4 (Expansions): Time to Response(Up to 1 year)
- Groups 3 and 4 (Expansions): Duration of Response(Up to 1 year)
- Groups 1 and 2: Time of Minimum or Trough Plasma Concentration (Tmin) of SY-5609(Predose, 0.5, 1, 2, 4, 6, 8 hours postdose on Day 1 and 4 or 15 of Cycle 1; 24 hours predose on Day 2 and 5 of Cycle 1; 24 hours predose on Day 1 of Cycle 2, 3 and 4 (Each Cycle=28 days))
- Groups 3 and 4 (Safety Lead-ins): Progression Free Survival(Up to 1 year)
- Groups 3 and 4 (Expansions): Objective Response Rate(Up to 1 year)
- Groups 3 and 4 (Safety Lead-ins): Complete Response/Remission (CR) Rate(Up to 1 year)
- Groups 3 and 4 (Safety Lead-ins): Disease Control Rate(Up to 1 year)
- Groups 3 and 4 (Safety Lead-ins): Time to Response(Up to 1 year)