A Phase 2 Basket Study of Tucatinib in Combination With Trastuzumab in Subjects With Previously Treated, Locally Advanced Unresectable or Metastatic Solid Tumors Driven by HER2 Alterations
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 217
- 试验地点
- 195
- 主要终点
- Confirmed Objective Response Rate (cORR) as Assessed by Investigator
研究概览
简要总结
This trial studies how well tucatinib works for solid tumors that make either more HER2 or a different type of HER2 than usual (HER2 alterations) The solid tumors studied in this trial have either spread to other parts of the body (metastatic) or cannot be removed completely with surgery (unresectable).
All participants will get both tucatinib and trastuzumab. People with hormone-receptor positive breast cancer will also get a drug called fulvestrant.
The trial will also look at what side effects happen. A side effect is anything a drug does besides treating cancer.
详细描述
There are multiple cohorts in this trial:
- 5 tumor specific cohorts with HER2 overexpression/amplification (cervical cancer, uterine cancer, biliary tract cancer, urothelial cancer, and non-squamous non-small cell lung cancer [NSCLC])
- 2 tumor specific cohorts with HER2 mutations (non-squamous NSCLC and breast cancer)
- 2 cohorts which will enroll all other HER2 amplified/overexpressed solid tumor types (except breast cancer, gastric or gastroesophageal junction adenocarcinoma [GEC], and colorectal cancer [CRC]) or HER2-mutated solid tumor types.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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 or cytologically confirmed diagnosis of locally-advanced unresectable or metastatic solid tumor, including primary brain tumors
- •Participants with non-squamous NSCLC must have progressed during or after standard treatment or for which no standard treatment is available
- •Participants with other disease types must have progressed during or after ≥1 prior line of systemic therapy for locally-advanced unresectable or metastatic disease
- •Disease progression during or after, or intolerance of, the most recent line of systemic therapy
- •Disease demonstrating HER2 alterations (overexpression/amplification or HER2 activating mutations), as determined by local or central testing processed in a Clinical Laboratory Improvement Amendments (CLIA)- or International Organization for Standardization (ISO) accredited laboratory, according to one of the following:
- •HER2 overexpression/amplification from fresh or archival tumor tissue or blood
- •Known activating HER2 mutations detected in fresh or archival tumor tissue or blood
- •Have measurable disease per RECIST v1.1 criteria according to investigator assessment
- •Have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
排除标准
- •Participants with breast cancer, gastric or gastroesophageal junction adenocarcinoma, or CRC whose disease shows HER2 amplification/overexpression.
- •Previous treatment with HER2-directed therapy; participants with uterine serous carcinoma or HER2-mutated gastric or gastroesophageal junction adenocarcinoma without HER2-overexpression/amplification may have received prior trastuzumab
- •Known hypersensitivity to any component of the drug formulation of tucatinib or trastuzumab (drug substance, excipients, murine proteins), or any component of the drug formulation of fulvestrant in participants with HR+ HER2-mutated breast cancer
- •History of exposure to a 360 mg/m² doxorubicin-equivalent or >720 mg/m^2 epirubicin-equivalent cumulative dose of anthracyclines
- •Treatment with any systemic anti-cancer therapy, radiation therapy, major surgery, or experimental agent within ≤3 weeks of first dose of study treatment or are currently participating in another interventional clinical trial.
- •There are additional inclusion and exclusion criteria. The study center will determine if criteria for participation are met.
研究组 & 干预措施
Tucatinib + Trastuzumab (+ Fulvestrant)
Tucatinib + trastuzumab (+ fulvestrant in hormone-receptor positive HER2-mutant breast cancer only)
干预措施: fulvestrant (Drug)
Tucatinib + Trastuzumab (+ Fulvestrant)
Tucatinib + trastuzumab (+ fulvestrant in hormone-receptor positive HER2-mutant breast cancer only)
干预措施: tucatinib (Drug)
Tucatinib + Trastuzumab (+ Fulvestrant)
Tucatinib + trastuzumab (+ fulvestrant in hormone-receptor positive HER2-mutant breast cancer only)
干预措施: trastuzumab (Drug)
结局指标
主要结局
Confirmed Objective Response Rate (cORR) as Assessed by Investigator
时间窗: From the first dose of study treatment until the first documented CR or PR on or before the first documented PD or new anti-cancer therapies or death, whichever occurred first (up to 28.3 months)
Confirmed ORR was defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version (v)1.1 as assessed by investigator and was considered as confirmed when subsequent response was at least 4 weeks after initial response. As per RECIST v1.1, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeter (mm). PR: at least a greater than or equal to (\>=)30 % decrease in the sum of diameters (SOD) of target lesions (longest for non-nodal target lesions and the short axes for nodal target lesions), taking as reference the baseline sum diameters. Disease progression (PD): at least \>=20% relative increase in SOD of target lesion taking as reference the smallest sum on study (including baseline sum if that is the smallest on study).
次要结局
- Confirmed Disease Control Rate (DCR) as Assessed by Investigator(From the first dose study treatment until PD or death, whichever occurred first (approximately 52.7 months))
- Duration of Response (DOR) as Assessed by Investigator(From the first documented CR or PR until the first documentation of PD or death or censoring date, whichever occurred first (approximately 52.7 months))
- Progression-Free Survival (PFS) as Assessed by Investigator(From the first documented CR or PR until the first documentation of PD or death or censoring date, whichever occurred first (approximately 52.7 months))
- Overall Survival (OS)(From date of start of study treatment until date of death or censoring date (approximately 52.7 months))
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)(From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 52.7 months))
- Number of Participants With Treatment Emergent Laboratory Test Abnormalities(From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 52.7 months))
- Number of Participants With Any Dose Modifications Due to AEs(From first dose of the study treatment (Day 1) up to the last dose of study treatment (approximately 52.7 months))
- Number of Participants With TEAEs of Special Interest(From first dose of the study treatment (Day 1) up to the last dose of study treatment (approximately 52.7 months))
- Maximum Concentration (Cmax) of Tucatinib(Cycle 3 Day 1: anytime within 1-4 hours post-dose)
- Trough Concentration (Ctrough) of Tucatinib(Cycle 3 Day 1: Predose)