A Phase 1a/1b Dose Escalation, Dose Expansion Study of SW-682 in Participants With Advanced Solid Tumors Enriched for Those With Hippo Pathway Mutations
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 186
- 试验地点
- 8
- 主要终点
- Maximum Tolerated Dose (Part 1 Only)
研究概览
简要总结
This is a first-in-human (FIH), Phase 1a/1b open-label, multicenter, dose escalation and dose expansion study of SW-682 in adult participants with metastatic or unresectable advanced solid tumors with or without Hippo pathway alterations that are refractory to, or have progressed, during or after appropriate prior systemic anticancer therapy, including chemotherapy, immunotherapy, radiation therapy or targeted therapy, or for which no treatment is available, or prior standard of care (SOC) therapy was not tolerated and for which there is no further SOC treatment available. The study includes a Part 1 (Phase 1a) dose escalation phase and a Part 2 (Phase 1b) dose expansion to optimize the dose to be used for further development. All participants will self-administer SW-682 by mouth in 28-day cycles.
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
- •Histologically confirmed, metastatic, or unresectable solid cancer that has either not responded to or progressed during or after appropriate prior systemic anticancer therapy including chemotherapy, immunotherapy, radiation therapy, or appropriate targeted therapy, or for which there is no treatment available or prior SOC therapy was not tolerated and for which there is no further SOC treatment available
- •Part 1: must have one of the following:
- •Mesothelioma with or without NF2 mutations
- •Advanced solid tumors with NF2 mutations
- •Advanced solid tumors with other Hippo pathway mutations or fusions (e.g., FAT1, LATS1/2, YAP fusions; WWTR1-CAMTA1 in EHE).
- •Part 2: must have the tumor histology and oncogenic mutation or genomic aberration specific to each dose expansion cohort defined below:
- •Cohort 1: Participants with mesothelioma with or without NF2 mutations
- •Cohort 2: Participants with advanced solid tumors with NF2 mutations
- •Cohort 3: Participants with advanced solid tumors with other Hippo pathway mutations identified during Part 1 (Phase 1a) dose escalation
- •Cohort 4: SW-682 with appropriate combination therapy.
- •In both parts, participants should have known oncogenic mutation identified by Next Generation Sequencing or local assay
- •Must have archival tumor tissue or agree to a fresh tumor biopsy at screening
- •Measurable disease per RECIST 1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
- •Adequate bone marrow, kidney, hepatic, and coagulation function
排除标准
- •Evidence of symptomatic CNS metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression
- •Clinically significant cardiac disease or abnormal cardiac parameters
- •Preexistence or inheritance of a familial renal syndrome
- •Concomitant non-anti-arrhythmic medications that are known to prolong the QTc interval
- •Concomitant medicines that are known strong/moderate inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) and/or CYP1A2 within 14 days or 5 half-lives before the first dose of study treatment
- •Concomitant medicines that are known sensitive substrates of CYP3A4, CYP2C19, CYP2D6, CYP1A2, and/or CYP2B6 within 14 days or 5 half-lives before the first dose of study treatment
- •Concomitant medicines that are known sensitive substrates of PGP, BCRP, OATP1B1, OATP1B3, OAT1, OAT3, MATE1, MATE2-K, OCT2
- •Clinically significant active infection (bacterial, fungal, or viral)
研究组 & 干预措施
Part 2 Dose Expansion Cohort 3
Participants with advanced solid tumors with other Hippo pathway mutations identified during Part 1 (Phase 1a) dose escalation will receive SW-682 tablets administered orally in continuous 28-day cycles at the recommended dose for expansion, based on Part 1 data.
干预措施: SW-682 (Drug)
Part 2 Dose Expansion Cohort 4
Participants will receive SW-682 tablets administered orally in continuous 28-day cycles at the recommended dose for expansion, based on Part 1 data, with appropriate combination therapy, identified based on Part 1 data.
干预措施: SW-682 (Drug)
Part 2 Dose Expansion Cohort 1
Participants with mesothelioma with or without NF2 mutations will receive SW-682 tablets administered orally in continuous 28-day cycles at the recommended dose for expansion, based on Part 1 data.
干预措施: SW-682 (Drug)
Phase 1 Dose Escalation Cohorts Ranging in Dose
Participants with advanced solid tumors with or without Hippo pathway mutations will receive SW-682 tablets administered orally in continuous 28-day cycles. SW-682 dosage and frequency of administration will vary by cohort.
干预措施: SW-682 (Drug)
Part 2 Dose Expansion Cohort 4
Participants will receive SW-682 tablets administered orally in continuous 28-day cycles at the recommended dose for expansion, based on Part 1 data, with appropriate combination therapy, identified based on Part 1 data.
干预措施: Combination Therapy (Drug)
Part 2 Dose Expansion Cohort 2
Participants with advanced solid tumors with NF2 mutations will receive SW-682 tablets administered orally in continuous 28-day cycles at the recommended dose for expansion, based on Part 1 data.
干预措施: SW-682 (Drug)
结局指标
主要结局
Maximum Tolerated Dose (Part 1 Only)
时间窗: Up to 24 months
The maximum tolerated dose (MTD) for SW-682, if any, will be based on safety and tolerability during the first 28 days of treatment in Cycle 1.
Recommended Dose for Expansion (Part 1 Only)
时间窗: Up to 24 months
The recommended dose for expansion (RDE) will be determined based on all safety, tolerability, pharmacokinetics (PK), preliminary antitumor efficacy, and other available data from Part 1 of the study.
Objective Response Rate (Part 2 Only)
时间窗: Up to 24 months
Objective response rate (ORR), defined as the proportion of participants with confirmed CR or PR using RECIST v1.1, mRECIST for mesothelioma, and/or GCIG CA-125 for ovarian cancer, as applicable, assessed by the investigator.
Incidence of Adverse Events (Part 1 Only)
时间窗: Up to 24 months
Safety and tolerability endpoint evaluation via incidence of dose limiting toxicities (DLTs), serious adverse events (SAEs), treatment emergent adverse events (TEAE)
次要结局
- Objective Response Rate (Part 1 Only)(Up to 24 months)
- Disease Control Rate(Up to 24 months)
- Duration of Response(Up to 24 months)
- Progression-Free Survival(Up to 24 months)
- Change in plasma and urine concentrations of SW-682(Up to 24 months)