Canadian clinical trial registry

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Study Description

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.

Cohort A: ROS1 fusion-positive tumors - Open

Participants with metastatic or advanced solid tumors, with the exception of NSCLC will receive entrectinib once daily in repeated 28-day cycles at a dose of 600 milligram per day (mg/day) for pediatric participants with a body surface area (BSA) >/= 1.51 m²

Cohort B: Cohort B: NTRK1/2/3 fusion-positive tumors - Open

Participants with metastatic or advanced solid tumors will receive entrectinib once daily in repeated 28-day cycles at a dose of 600 mg/day for adults and pediatric participants with a BSA >/= 1.51 m²

Cohort C: ALK fusion-positive tumors (excluding NSCLC) - Open

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.

Cohort D: TMB-high tumors - Open

Participants with metastatic or advanced solid tumors will receive atezolizumab intravenously (IV) at a dose of 15 mg/kg (maximum 1200 mg) for participants aged < 18 years on Day 1 of each 21-day cycle.

Cohort E: AKT1/2/3 mutant-positive tumors - Closed to Accrual

Participants with metastatic or advanced solid tumors will receive ipatasertib orally once daily (QD). For participants 12-17 years of age, ipatasertib will be administered at the starting dose of 200 mg for participants <35 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.

Cohort F: HER2 mutant-positive tumors - Closed to Accrual

Participants with metastatic or advanced solid tumors will receive trastuzumab emtansine IV at a dose of 3.6 mg/kg every 21 days. This dosage and administration method also applies for pediatric participants 12-17 years of age.

Cohort H: PIK3CA multiple mutant-positive tumors - Open

Participants with metastatic or advanced solid tumors will receive GDC-0077 daily at a starting dose of 9 mg by mouth (PO) in repeated 28-day cycles. This dosage and administration method also applies for pediatric participants 12-17 years of age.

Cohort I: BRAF class II mutant or fusion-positive tumors - Open

Participants with BRAF class II mutant/fusion-positive tumors (adults and adolescents ≥ 40 kg) will receive 400 mg belvarafenib by mouth (PO) BID (twice a day) 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.

Cohort J: BRAF class III mutant-positive tumors - Open

Participants with BRAF class III mutant-positive tumors (adults and adolescents ≥ 40 kg) will receive 400 mg belvarafenib by mouth (PO) BID (twice a day) 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.

Cohort K: RET fusion-positive tumors - Open

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 patients ≥ 12 and < 18 years of age. A treatment cycle consists of 4 weeks (28 days).

Inclusion Criteria

• In addition to the general inclusion criteria below, participants must meet all of the cohort-specific inclusion criteria for the respective cohort
• Briefly - for arm A, a ROS1 fusion is required; for arm B, a NTRK1/2/3 fusion is required; for arm D, a TMB >16mut/Mb is required; for arm E: specific mutations in the AKT gene are required; for arm F: specific mutations in the HER2 gene are required; for arm H, specific mutations in the PIK3CA gene are required; for arm I, a BRAF Class II mutation or fusion is required; for arm J, a BRAF Class III mutation is required; for Cohort K; a RET fusion is required. 
• Histologically or cytologically confirmed diagnosis of advanced and unresectable or metastatic solid malignancy
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), Response Assessment in Neuro-Oncology (RANO) criteria, or International Neuroblastoma Response Criteria (INRC)
• Performance status as follows: Participants aged >= 18 years: Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2; Participantss 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

Exclusion Criteria

• 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

Multiple other inclusion and exclusion criteria could apply and will be reviewed by your treating team