MyTACTIC: An Open-Label Phase II Study Evaluating Targeted Therapies in Patients Who Have Advanced Solid Tumors With Genomic Alterations or Protein Expression Patterns Predictive of Response
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 252
- 试验地点
- 38
- 主要终点
- Confirmed Objective Response Rate (ORR) Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria for Primary Central Nervous System (CNS) Tumors
研究概览
简要总结
This is a Phase II, multicenter, non-randomized, open-label, multi-arm study designed to evaluate the safety and efficacy of targeted therapies as single agents or in rational, specified combinations in participants with advanced unresectable or metastatic solid tumors determined to harbor specific biomarkers.
Patients will be enrolled based on local testing performed at a Clinical Laboratory Improvement Amendments (CLIA)-certified or equivalently accredited diagnostic laboratory. The multi-arm structure of the MyTACTIC study allows patients with solid tumors to be treated with a drug or drug regimen tailored to their biomarker identified at screening.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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 advanced unresectable or metastatic solid malignancy
- •Positive biomarker results from a Clinical Laboratory Improvement Amendments (CLIA)-certified or equivalently accredited diagnostic laboratory and availability of a full report of the testing results. This may be from a tissue or blood sample.
- •Evaluable or measurable disease
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- •Life expectancy ≥8 weeks
- •Adequate hematologic and end-organ function, as defined in the protocol, obtained within 14 days prior to initiation of study treatment
- •Agrees to take measures to prevent pregnancy in the patient or partner
- •In addition to the general inclusion criteria above, there are treatment-specific inclusion criteria that apply for each respective treatment arm (as detailed in the protocol)
排除标准
- •Current participation or enrollment in another therapeutic clinical trial
- •Symptomatic or actively progressing CNS metastases (asymptomatic patients with treated or untreated CNS metastases may be eligible, provided all protocol-defined criteria are met)
- •History of leptomeningeal disease, unless noted otherwise for a specific treatment arm of the study
- •Wide field radiotherapy within 14 days prior to start of study treatment
- •Stereotactic radiosurgery within 7 days prior to start of study treatment
- •Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infections, or any active infection that, in the opinion of the investigator, could impact patient safety
- •Receipt of any anticancer drug/biologic or investigational treatment 21 days prior to Cycle 1, Day 1 except hormone therapy, which can be given up to 7 days prior to Cycle 1, Day 1 (androgen blockage may be continued for male patients with prostate cancer)
- •Known human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) infection with status outside of study-allowed criteria
- •History of or concurrent serious medical condition or abnormality in clinical laboratory tests that precludes the patient's safe participation in and completion of the study or confounds the ability to interpret data from the study
- •History of malignancy other than disease under study within 3 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
- •Incomplete recovery from any surgery prior to the start of study treatment that would interfere with the determination of safety or efficacy of study treatment
- •Major surgical procedure, other than for diagnosis, or significant traumatic injury within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
- •Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or higher), myocardial infarction, or cerebrovascular accident within 3 months prior to enrollment, unstable arrhythmias, or unstable angina
- •Pregnant or breastfeeding, or intending to become pregnant during the study
- •In addition to the general exclusion criteria above, there are treatment-specific exclusion criteria that apply for each respective treatment arm (as detailed in the protocol)
研究组 & 干预措施
Arm A: Entrectinib
Participants in this treatment arm must have a positive tumor biomarker result for ROS1 gene fusion.
干预措施: Entrectinib (Drug)
Arm B: Inavolisib
Participants in this treatment arm must have a positive tumor biomarker result for PI3KCA activating mutation.
干预措施: Inavolisib (Drug)
Arm C: Alectinib
Participants in this treatment arm must have a positive tumor biomarker result for ALK rearrangement tumors.
干预措施: Alectinib (Drug)
Arm D: Ipatasertib
Participants in this treatment arm must have a positive tumor biomarker result for either AKT1/2/3 activating mutation or PTEN loss/loss of function.
干预措施: Ipatasertib (Drug)
Arm E: Atezolizumab + Investigator's Choice of Chemotherapy
Participants in this treatment arm must have a positive tumor biomarker result for either tumor mutational burden (TMB) high or microsatellite instability (MSI) high/deficient mismatch repair (dMMR).
干预措施: Atezolizumab (Drug)
Arm E: Atezolizumab + Investigator's Choice of Chemotherapy
Participants in this treatment arm must have a positive tumor biomarker result for either tumor mutational burden (TMB) high or microsatellite instability (MSI) high/deficient mismatch repair (dMMR).
干预措施: Investigator's Choice of Chemotherapy (Drug)
Arm F: Trastuzumab Emtansine + Atezolizumab
Participants in this treatment arm must have a positive tumor biomarker result for human epidermal growth factor receptor 2 (HER2) mutations or amplification without known TMB high or MSI high/dMMR.
干预措施: Atezolizumab (Drug)
Arm F: Trastuzumab Emtansine + Atezolizumab
Participants in this treatment arm must have a positive tumor biomarker result for human epidermal growth factor receptor 2 (HER2) mutations or amplification without known TMB high or MSI high/dMMR.
干预措施: Trastuzumab Emtansine (Drug)
Arm G: PH FDC SC
Participants in this treatment arm must have a positive tumor biomarker result for HER2 mutation or amplification without known TMB high or MSI high/dMMR.
干预措施: Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf (Drug)
Arm H: PH FDC SC + Investigator's Choice of Chemotherapy
Participants in this treatment arm must have a positive tumor biomarker result for HER2 mutation or amplification without known TMB high or MSI high/dMMR.
干预措施: Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf (Drug)
Arm H: PH FDC SC + Investigator's Choice of Chemotherapy
Participants in this treatment arm must have a positive tumor biomarker result for HER2 mutation or amplification without known TMB high or MSI high/dMMR.
干预措施: Investigator's Choice of Chemotherapy (Drug)
Arm I: Trastuzumab Emtansine + Tucatinib
Participants in this treatment arm must have a positive tumor biomarker result for HER2 mutation or amplification without known TMB high or MSI high/dMMR.
干预措施: Trastuzumab Emtansine (Drug)
Arm I: Trastuzumab Emtansine + Tucatinib
Participants in this treatment arm must have a positive tumor biomarker result for HER2 mutation or amplification without known TMB high or MSI high/dMMR.
干预措施: Tucatinib (Drug)
Arm J: Trastuzumab Emtansine + Atezolizumab
Participants in this treatment arm must have positive tumor biomarker results for HER2 mutation or amplification and TMB high or MSI high/dMMR.
干预措施: Atezolizumab (Drug)
Arm J: Trastuzumab Emtansine + Atezolizumab
Participants in this treatment arm must have positive tumor biomarker results for HER2 mutation or amplification and TMB high or MSI high/dMMR.
干预措施: Trastuzumab Emtansine (Drug)
Arm K: Ipatasertib + Atezolizumab
Participants in this treatment arm must have a positive tumor biomarker result for PI3KCA activating mutation.
干预措施: Ipatasertib (Drug)
Arm K: Ipatasertib + Atezolizumab
Participants in this treatment arm must have a positive tumor biomarker result for PI3KCA activating mutation.
干预措施: Atezolizumab (Drug)
Arm L: Ipatasertib + Atezolizumab
Participants in this treatment arm must have a positive tumor biomarker result for either AKT1/2/3 activating mutation or PTEN loss/loss of function.
干预措施: Ipatasertib (Drug)
Arm L: Ipatasertib + Atezolizumab
Participants in this treatment arm must have a positive tumor biomarker result for either AKT1/2/3 activating mutation or PTEN loss/loss of function.
干预措施: Atezolizumab (Drug)
Arm M: Ipatasertib + Paclitaxel
Participants in this treatment arm must have a positive tumor biomarker results for PI3KCA activating mutations and either AKT1/2/3 activating mutation or PTEN loss/loss of function.
干预措施: Ipatasertib (Drug)
Arm M: Ipatasertib + Paclitaxel
Participants in this treatment arm must have a positive tumor biomarker results for PI3KCA activating mutations and either AKT1/2/3 activating mutation or PTEN loss/loss of function.
干预措施: Paclitaxel (Drug)
Arm N: Atezolizumab + Tiragolumab
Participants in this treatment arm must have a positive tumor biomarker result for either TMB high or MSI high/dMMR.
干预措施: Atezolizumab (Drug)
Arm N: Atezolizumab + Tiragolumab
Participants in this treatment arm must have a positive tumor biomarker result for either TMB high or MSI high/dMMR.
干预措施: Tiragolumab (Drug)
Arm O: Pralsetinib
Participants in this treatment arm must have a positive tumor biomarker result for RET fusion.
干预措施: Pralsetinib (Drug)
结局指标
主要结局
Confirmed Objective Response Rate (ORR) Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria for Primary Central Nervous System (CNS) Tumors
时间窗: Up to 32 months
Confirmed objective response rate (cORR)=percentage of participants with best response as complete response (CR) or partial response (PR) for measurable disease \& CR for non-measurable disease. Confirmation=CR/PR on 2 consecutive visits ≥4 weeks apart for 3-week cycles \& ≥6 weeks apart for 4-week cycles. Per RECIST, CR=disappearance of all target lesions. PR= ≥30% decrease in sum of diameters of target lesions, in absence of CR. Per RANO, CR=complete disappearance of all measurable \& non-measurable disease for ≥4 weeks; no new lesions/abnormality on T2/FLAIR imaging; stable/improved non-enhancing lesions; participants must be off corticosteroids or on physiological doses; clinical status stable/improved. PR= ≥50% decrease in the sum of products of perpendicular diameters of measurable enhancing lesions on T2/FLAIR imaging for ≥4 weeks; no progression of non-measurable T1 disease; stable/improved non-enhancing lesions; corticosteroid dose ≤ baseline; clinical status stable/improved.
次要结局
- Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria(Time from start of treatment to the first occurrence of disease progression or death from any cause (Up to 32 months))
- Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria(Time from the date of the first confirmed CR/PR to PD or death from any cause (Up to 32 months))
- PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria(At Months 3, 6, 9 and 12)
- Percentage of Participants With Disease Control, as Determined by the Investigator According to RECIST v1.1 or RANO Criteria(Up to 32 months)
- Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0)(From initiation of study drug until 28 days after the final dose of study drugs other than atezolizumab and until 90 days after the final dose of atezolizumab (Up to 32 months))