Tumor-agnostic Precision Immuno-oncology and Somatic Targeting Rational for You (TAPISTRY) Phase II Platform Trial
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 920
- 试验地点
- 225
- 主要终点
- All Cohorts: Independent Review Committee (IRC)-assessed Objective Response Rate (ORR) Based on Confirmed Objective Response (OR) per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
研究概览
简要总结
TAPISTRY is a Phase II, global, multicenter, open-label, multi-cohort study designed to evaluate the safety and efficacy of targeted therapies or immunotherapy as single agents or in rational, specified combinations in participants with unresectable, locally advanced or metastatic solid tumors determined to harbor specific oncogenic genomic alterations or who are tumor mutational burden (TMB)-high as identified by a validated next-generation sequencing (NGS) assay. Participants with solid tumors will be treated with a drug or drug regimen tailored to their NGS assay results at screening. Participants will be assigned to the appropriate cohort based on their genetic alteration(s). Treatment will be assigned on the basis of relevant oncogenotype, will have cohort-specific inclusion/exclusion criteria, and, unless otherwise specified, will continue until disease progression, loss of clinical benefit, unacceptable toxicity, participant or physician decision to discontinue, or death, whichever occurs first.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed diagnosis of advanced and unresectable or metastatic solid malignancy
- •Measurable disease as defined by RECIST v1.1, RANO, or INRC
- •Performance status as follows: Participants aged ≥ 18 years: Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2; Participants aged 16 to < 18 years: Karnofsky score ≥ 50%; Participants aged < 16 years: Lansky score ≥ 50%
- •For participants aged ≥ 18 and < 18 years: adequate hematologic and end-organ function
- •Disease progression on prior treatment, or previously untreated disease with no available acceptable treatment
- •Adequate recovery from most recent systemic or local treatment for cancer
- •Life expectancy ≥ 8 weeks
- •Ability to comply with the study protocol, in the investigator's judgment
- •For female participants of childbearing potential: Negative serum pregnancy test ≤ 14 days prior to initiating study treatment, agreement to remain abstinent or use single or combined contraception methods that result in a failure rate of < 1% per year for the period defined in the cohort-specific inclusion criteria; and agreement to refrain from donating eggs during the same period
- •For male participants: Willingness to remain abstinent or use acceptable methods of contraception as defined in the cohort-specific inclusion criteria
- •In addition to the general inclusion criteria above, participants must meet all of the cohort-specific inclusion criteria for the respective cohort
排除标准
- •Current participation or enrollment in another therapeutic clinical trial
- •Any anticancer treatment within 2 weeks or 5 half-lives prior to start of study treatment
- •Whole brain radiotherapy within 14 days prior to start of study treatment
- •Stereotactic radiosurgery within 7 days prior to start of study treatment
- •Pregnant or breastfeeding, or intending to become pregnant during the study
- •History of or concurrent serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study or confounds the ability to interpret data from the study
- •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
- •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
- •History of another active cancer within 5 years prior to screening that may interfere with the determination of safety or efficacy of study treatment with respect to the qualifying solid tumor malignancy
- •In addition to the general exclusion criteria above, in order to be enrolled in a treatment cohort of the study, participants must not meet any of the cohort-specific exclusion criteria
研究组 & 干预措施
Cohort H: PIK3CA Multiple Mutant-positive Tumors
Participants with phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) multiple mutant-positive tumors will receive inavolisib (GDC-0077) QD at a starting dose of 9 mg by mouth (PO) in repeated 28-day cycles. Note: Cohort H has been closed for enrollment.
干预措施: Inavolisib (Drug)
Cohort J: BRAF Class III Mutant-positive Tumors
Participants with BRAF class III mutant-positive tumors (adults and adolescents ≥ 40 kg) will receive 400 mg belvarafenib PO BID with adequate water (more than 200 mL). One cycle consists of 28 days. Administration of belvarafenib should occur BID on every day of each 28-day cycle. Note: Cohort J has been closed for enrollment.
干预措施: Belvarafenib (Drug)
Cohort L: KRAS G12C-positive Tumors (Excluding NSCLC and Colorectal Cancer [CRC])
Participants with kirsten rat sarcoma virus (KRAS) G12C-positive tumors will self-administer divarasib (GDC-6036) orally at home (except on clinic days).
干预措施: Divarasib (Drug)
Cohort E: Protein Kinase B (AKT) 1/2/3 Mutant-positive Tumors
Participants with metastatic or advanced solid tumors will receive ipatasertib orally, QD at the starting dose of 400 mg in repeated 28-day cycles until the participant experiences disease progression, intolerable toxicity, or withdraws consent. For participants 12-17 years of age, ipatasertib will be administered at the starting dose of 200 mg for participants < 35 kilograms (kg), 300 mg for participants ≥ 35 and < 45 kg, 400 mg for those ≥ 45 kg orally QD in repeated 28-day cycles until the participant experiences disease progression, intolerable toxicity, or withdraws consent. Note: Cohort E has been closed.
干预措施: Ipatasertib (Drug)
Cohort I: BRAF Class II Mutant or Fusion-positive Tumors
Participants with proto-oncogene B-Raf (BRAF) class II mutant/fusion-positive tumors (adults and adolescents ≥ 40 kg) will receive 400 mg belvarafenib, PO, BID with adequate water (more than 200 milliliters [mL]). One cycle consists of 28 days. Administration of belvarafenib should occur BID on every day of each 28-day cycle. Note: Cohort I has been closed.
干预措施: Belvarafenib (Drug)
Cohort B: Neurotrophic Tyrosine Receptor Kinase (NTRK) 1/2/3 Fusion-positive Tumors
Participants with metastatic or advanced solid tumors will receive entrectinib, QD in repeated 28-day cycles at a dose of 600 mg/day for adults and pediatric participants with a BSA ≥ 1.51 m^2. The total dose of daily entrectinib administration for pediatric participants with BSA < 1.51 m^2 will be lower.
干预措施: Entrectinib (Drug)
Cohort K: Rearranged During Transfection (RET) Fusion-positive Tumors (Excluding NSCLC)
Participants with RET fusion-positive tumors will self-administer pralsetinib orally at home (except on clinic days) on a continuous daily dosing regimen at a dose of 400 mg/day (four 100-mg capsules per day) for adult and pediatric participants ≥ 12 and < 18 years of age. A treatment cycle consists of 4 weeks (28 days). Note: Cohort K has been closed.
干预措施: Pralsetinib (Drug)
Cohort M: Ataxia-telangiectasia Mutated (ATM) Loss of Function (LOF) Tumors
Participants with ATM LOF tumors will self-administer camonsertib orally at home (except on clinic days). Note: Cohort M has been closed.
干预措施: Camonsertib (Drug)
Cohort C: Anaplastic Lymphoma Kinase (ALK) Fusion-positive Tumors (Excluding NSCLC)
Participants with metastatic or advanced solid tumors, with the exception of NSCLC, will receive alectinib at a dosage of 600 mg, orally, twice a day (BID), taken with food, in repeated 28-day cycles.
干预措施: Alectinib (Drug)
Cohort A: ROS Proto-oncogene 1 (ROS1) Fusion-positive Tumors (Excluding NSCLC)
Participants with metastatic or advanced solid tumors, with the exception of non-small cell lung cancer (NSCLC), will receive entrectinib once daily (QD) in repeated 28-day cycles at a dose of 600 milligram per day (mg/day) for adults and pediatric participants with a body surface area (BSA) ≥ 1.51 square meter (m^2). The total dose of daily entrectinib administration for pediatric participants with BSA < 1.51 m^2 will be lower.
干预措施: Entrectinib (Drug)
Cohort D: TMB-high Tumors
Participants with metastatic or advanced solid tumors will receive atezolizumab intravenously (IV) at a fixed dose for participants aged ≥ 18 years, and 15 milligrams per kilogram (mg/kg) (maximum 1200 mg) for participants aged < 18 years on Day 1 of each 21-day cycle. Note: Cohort D has been closed.
干预措施: Atezolizumab (Drug)
Cohort F: Human Epidermal Growth Factor Receptor 2 (HER2) Mutant-positive Tumors
Participants with metastatic or advanced solid tumors will receive trastuzumab emtansine IV at a dose of 3.6 mg/kg every 21 days.
Note: Cohort F has been closed as of protocol version 7 because enrollment and participant follow-up have been completed.
干预措施: Trastuzumab emtansine (Drug)
Cohort N: SETD2 LOF Tumors
Participants with methyltransferase SET (Su(var) 3-9) Enhancer of zest and Trithorax) domain-containing 2 (SETD2) LOF tumors will self-administer camonsertib orally at home (except on clinic days). Note: Cohort N has been closed.
干预措施: Camonsertib (Drug)
结局指标
主要结局
All Cohorts: Independent Review Committee (IRC)-assessed Objective Response Rate (ORR) Based on Confirmed Objective Response (OR) per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
时间窗: Approximately up to 12 years
Confirmed objective response indicates ≥4 weeks after initial documentation of response.
次要结局
- All Cohorts: IRC-assessed Duration of Response (DOR) per RECIST v1.1(Approximately up to 12 years)
- All Cohorts: IRC-assessed Clinical Benefit Rate (CBR) per RECIST v1.1(Approximately up to 12 years)
- All Cohorts: IRC-assessed Progression-free Survival (PFS) per RECIST v1.1(Approximately up to 12 years)
- All Cohorts: Investigator (INV)-assessed ORR per RECIST v1.1(Approximately up to 12 years)
- All Cohorts: INV-assessed DOR per RECIST v1.1(Approximately up to 12 years)
- All Cohorts: INV-assessed CBR per RECIST v1.1(Approximately up to 12 years)
- All Cohorts: INV-assessed PFS per RECIST v1.1(Approximately up to 12 years)
- All Cohorts: IRC- and INV-assessed Time to Central Nervous System (CNS) Progression per RECIST v1.1(Approximately up to 12 years)
- All Cohorts: Overall Survival (OS)(Approximately up to 12 years)
- Cohorts A, B, C, D, I, J, K: IRC-assessed CNS-ORR per Response Assessment in Neuro-oncology (RANO)(Approximately up to 12 years)
- Cohorts A, B, C, D, I, J, K: IRC-assessed CNS-DOR per RANO(Approximately up to 12 years)
- Cohorts A, B, C, D, I, J, K: IRC-assessed CNS-CBR per RANO(Approximately up to 12 years)
- Cohorts A, B, C, D, I, J, K: IRC-assessed CNS-PFS per RANO(Approximately up to 12 years)
- Cohorts A, B, C, D, I, J, K: INV-assessed CNS-ORR per RANO(Approximately up to 12 years)
- Cohorts A, B, C, D, I, J, K: INV-assessed CNS-DOR per RANO(Approximately up to 12 years)
- Cohorts A, B, C, D, I, J, K: INV-assessed CNS-CBR per RANO(Approximately up to 12 years)
- Cohorts A, B, C, D, I, J, K: INV-assessed CNS-PFS per RANO(Approximately up to 12 years)
- Cohorts A, B, C, D, E, F, H, I, J, K, L, M, N: IRC-assessed ORR per International Neuroblastoma Response Criteria (INRC)(Approximately up to 12 years)
- Cohorts A, B, C, D, E, F, H, I, J, K, L, M, N: IRC-assessed DOR per INRC(Approximately up to 12 years)
- Cohorts A, B, C, D, E, F, H, I, J, K, L, M, N: IRC-assessed CBR per INRC(Approximately up to 12 years)
- Cohorts A, B, C, D, E, F, H, I, J, K, L, M, N: IRC-assessed PFS per INRC(Approximately up to 12 years)
- Cohorts A, B, C, D, E, F, H, I, J, K, L, M, N: INV-assessed ORR per INRC(Approximately up to 12 years)
- Cohorts A, B, C, D, E, F, H, I, J, K, L, M, N: INV-assessed DOR per INRC(Approximately up to 12 years)
- Cohorts A, B, C, D, E, F, H, I, J, K, L, M, N: INV-assessed CBR per INRC(Approximately up to 12 years)
- Cohorts A, B, C, D, E, F, H, I, J, K, L, M, N: INV-assessed PFS per INRC(Approximately up to 12 years)
- Cohorts A, B, C, D, I, J, K: IRC-assessed Intracranial (IC)-ORR per RECIST v1.1(Approximately up to 12 years)
- Cohorts A, B, C, D, I, J, K: IRC-assessed IC-DOR per RECIST v1.1(Approximately up to 12 years)
- Cohorts A, B, C, D, I, J, K: IRC-assessed IC-CBR per RECIST v1.1(Approximately up to 12 years)
- Cohorts A, B, C, D, I, J, K: IRC-assessed IC-PFS Rate per RECIST v1.1(Approximately up to 12 years)
- Cohorts A, B, C, D, I, J, K: INV-assessed IC-ORR per RECIST v1.1(Approximately up to 12 years)
- Cohorts A, B, C, D, I, J, K: INV-assessed IC-DOR per RECIST v1.1(Approximately up to 12 years)
- Cohorts A, B, C, D, I, J, K: INV-assessed IC-CBR per RECIST v1.1(Approximately up to 12 years)
- Cohorts A, B, C, D, I, J, K: INV-assessed IC-PFS Rate per RECIST v1.1(Approximately up to 12 years)
- Cohorts A and B: Percentage of Participants With Confirmed Deterioration as Assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)(Approximately up to 12 years)
- Cohorts A and B: Change From Baseline in the EORTC-QLQ-C30 Total Score(Approximately up to 12 years)
- Cohorts A and B: Percentage of Participants With a Clinical Meaningful Change on the Global Health Status, Physical Functioning, and Role Functioning Scores From the EORTC QLQ-C30(Approximately up to 12 years)
- Cohorts A and B: Time to Confirmed Symptom Onset or Worsening From Tumor-related Symptom Scores From the EORTC QLQ-C30 and EORTC Item Library 71 (IL71)(Approximately up to 12 years)
- All Cohorts: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Approximately up to 12 years)