Clinical Trials /

Tumor-Agnostic Precision Immuno-Oncology and Somatic Targeting Rational for You (TAPISTRY) Platform Study

NCT04589845

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Tumor-Agnostic Precision Immuno-Oncology and Somatic Targeting Rational for You (TAPISTRY) Platform Study
  • Official Title: Tumor-Agnostic Precision Immunooncology and Somatic Targeting Rational for You (TAPISTRY) Phase II Platform Trial

Clinical Trial IDs

  • ORG STUDY ID: BO41932
  • SECONDARY ID: 2020-001847-16
  • NCT ID: NCT04589845

Conditions

  • Solid Tumors

Interventions

DrugSynonymsArms
EntrectinibCohort A: ROS1 fusion-positive tumors
EntrectinibCohort B: NTRK1/2/3
AlectinibCohort C: ALK fusion-positive tumors
AtezolizumabCohort D: TMB-high tumors
IpatasertibCohort E: AKT1/2/3 mutant-positive tumors
Trastuzumab emtansineCohort F: HER2 mutant-positive tumors
IdasanutlinCohort G: MDM2-amplified, TP53 wild-type tumors
GDC-0077Cohort H: PIK3CA multiple mutant-positive tumors

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Cohort A: ROS1 fusion-positive tumorsExperimentalParticipants 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 adults and pediatric participants with a body surface area (BSA) >/= 1.51 squaremeter (m2). The total dose of daily entrectinib administration for pediatric participants with BSA<1.51 m2 will be lower.
  • Entrectinib
Cohort B: NTRK1/2/3ExperimentalParticipants 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. The total dose of daily entrectinib administration for pediatric participants with BSA<1.51 m2 will be lower.
  • Entrectinib
Cohort C: ALK fusion-positive tumorsExperimentalParticipants 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.
  • Alectinib
Cohort D: TMB-high tumorsExperimentalParticipants with metastatic or advanced solid tumors will receive atezolizumab intravenously (IV) at a fixed dose for participants aged >/= 18 years, and 15 mg/kg (maximum 1200 mg) for participants aged < 18 years on Day 1 of each 21-day cycle.
  • Atezolizumab
Cohort E: AKT1/2/3 mutant-positive tumorsExperimentalParticipants with metastatic or advanced solid tumors will receive ipatasertib orally once daily (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 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.
  • Ipatasertib
Cohort F: HER2 mutant-positive tumorsExperimentalParticipants with metastatic or advanced solid tumors will receive trastuzumab emtansine IV at a dose of 3.6 mg/kg every 21 days.
  • Trastuzumab emtansine
Cohort G: MDM2-amplified, TP53 wild-type tumorsExperimentalParticipants with metastatic or advanced solid tumors will receive idasanutlin at a dose of 250 mg orally QD on Days 1-5 of each 28-day cycle.
  • Idasanutlin
Cohort H: PIK3CA multiple mutant-positive tumorsExperimentalParticipants with metastatic or advanced solid tumors will receive GDC-0077 QD at a starting dose of 9 mg by mouth (PO) in repeated 28-day cycles.
  • GDC-0077

Eligibility Criteria

        Inclusion Criteria:

          -  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: Participantss 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

          -  In addition to the general inclusion criteria above, participants must meet all of the
             cohort-specific inclusion criteria for the respective cohort

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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)
Time Frame:Approximately up to 12 years
Safety Issue:
Description:Confirmed objective response indicates >/= 4 weeks after initial documentation of response

Secondary Outcome Measures

Measure:All Cohorts: IRC-assessed duration of response (DOR) per RECIST v1.1
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:All Cohorts: IRC-assessed clinical benefit rate (CBR) per RECIST v1.1
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:All Cohorts: IRC-assessed progression free survival (PFS) per RECIST v1.1
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:All Cohorts: Investigator (INV)-assessed ORR per RECIST v1.1
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:All Cohorts: INV-assessed DOR per RECIST v1.1
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:All Cohorts: INV-assessed CBR per RECIST v1.1
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:All Cohorts: INV-assessed PFS per RECIST v1.1
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:All Cohorts: IRC- and INV-assessed time to central nervous system (CNS) progression per RECIST v1.1
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:All Cohorts: Overall Survival (OS)
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:Cohorts A, B, C, D: IRC-assessed CNS-ORR per Response Assessment in Neuro-Oncology (RANO)
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:Cohorts A, B, C, D: IRC-assessed CNS-DOR per RANO
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:Cohorts A, B, C, D: IRC-assessed CNS-CBR per RANO
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:Cohorts A, B, C, D: IRC-assessed CNS-PFS per RANO
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:Cohorts A, B, C, D: INV-assessed CNS-ORR per RANO
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:Cohorts A, B, C, D: INV-assessed CNS-DOR per RANO
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:Cohorts A, B, C, D: INV-assessed CNS-CBR per RANO
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:Cohorts A, B, C, D: INV-assessed CNS-PFS per RANO
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:Cohorts A, B, D, E, F, G, H: IRC-assessed ORR per International Neuroblastoma Response Criteria (INRC)
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:Cohorts A, B, D, E, F, G, H: IRC-assessed DOR per INRC
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:Cohorts A, B, D, E, F, G, H: IRC-assessed CBR per INRC
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:Cohorts A, B, D, E, F, G, H: IRC-assessed PFS per INRC
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:Cohorts A, B, D, E, F, G, H: INV-assessed ORR per INRC
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:Cohorts A, B, D, E, F, G, H: INV-assessed DOR per INRC
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:Cohorts A, B, D, E, F, G, H: INV-assessed CBR per INRC
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:Cohorts A, B, D, E, F, G, H: INV-assessed PFS per INRC
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:All Cohorts: IRC-assessed ORR per RECIST v1.1 in participants with alteration/biomarker-positive circulating tumor DNA (ctDNA) by blood-based next-generation sequencing (NGS) assay
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:All Cohorts: IRC-assessed DOR per RECIST v1.1 in participants with alteration/biomarker-positive ctDNA by blood-based NGS assay
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:All Cohorts: IRC-assessed CBR per RECIST v1.1 in participants with alteration/biomarker-positive ctDNA by blood-based NGS assay
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:All Cohorts: IRC-assessed PFS per RECIST v1.1 in participants with alteration/biomarker-positive ctDNA by blood-based NGS assay
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:All Cohorts: INV-assessed ORR per RECIST v1.1 in participants with alteration/biomarker-positive ctDNA by blood-based NGS assay
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:All Cohorts: INV-assessed DOR per RECIST v1.1 in participants with alteration/biomarker-positive ctDNA by blood-based NGS assay
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:All Cohorts: INV-assessed CBR per RECIST v1.1 in participants with alteration/biomarker-positive ctDNA by blood-based NGS assay
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:All Cohorts: INV-assessed PFS per RECIST v1.1 in participants with alteration/biomarker-positive ctDNA by blood-based NGS assay
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:Cohorts A, B, C, D: IRC-assessed intracranial (IC)-ORR per RECIST v1.1
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:Cohorts A, B, C, D: IRC-assessed IC-DOR per RECIST v1.1
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:Cohorts A, B, C, D: IRC-assessed IC-CBR per RECIST v1.1
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:Cohorts A, B, C, D: IRC-assessed IC-PFS rate per RECIST v1.1
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:Cohorts A, B, C, D: INV-assessed IC-ORR per RECIST v1.1
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:Cohorts A, B, C, D: INV-assessed IC-DOR per RECIST v1.1
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:Cohorts A, B, C, D: INV-assessed IC-CBR per RECIST v1.1
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:Cohorts A, B, C, D: INV-assessed IC-PFS rate per RECIST v1.1
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:All Cohorts: Percentage of participants with confirmed deterioration as assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30)
Time Frame:Approximately up to 12 years
Safety Issue:
Description:The EORTC QLQ-C30 is a validated, reliable self-report measure. It consists of 30 questions that assess five aspects of participant functioning (physical, emotional, role, cognitive, and social), eight symptom scales (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea) and global health/quality of life, with a recall period of the previous week. Scale scores can be obtained for the multi-item scales using rating scales of 4 or 7 points.
Measure:All Cohorts: Change from Baseline in the EORTC-QLQ-C30 total score
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:All Cohorts: Percentage of participants with a clinical meaningful change on the Global Health Status, Physical Functioning, and Role Functioning scores from the EORTC QLQ-C30
Time Frame:Approximately up to 12 years
Safety Issue:
Description:
Measure:All Cohorts: Time to confirmed symptom onset or worsening from tumor-related symptom scores from the EORTC QLQ-C30 and EORTC Item Library
Time Frame:Approximately up to 12 years
Safety Issue:
Description:The EORTC Item library includes stand-alone symptoms scales and an overall assessment of treatment bother to provide additional information not currently captured in the EORTC QLQ-C30. The scales use the same rating scale and recall period of previous week as the symptom scales in the EORTC QLQ-C30.
Measure:All Cohorts: Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame:Approximately up to 12 years
Safety Issue:
Description:Adverse event severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5 (NCI CTCAE v5.0.)
Measure:Cohorts A, B: Plasma concentration of entrectinib at specified timepoints
Time Frame:Day 1 of Cycle 1-6 and Day 1 of every other Cycle going forward (one Cycle=28 days)
Safety Issue:
Description:
Measure:Cohort C: Plasma concentration of alectinib at specified timepoints
Time Frame:Cycle 1, Day 1 and Day 15; Day 1 of Cycle 2-6, and Day 1 of every other Cycle going forward (one Cycle=28 days)
Safety Issue:
Description:
Measure:Cohort D: Plasma concentration of atezolizumab at specified timepoints
Time Frame:Day 1 of Cycle 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, and every even Cycles thereafter (one Cycle=21 days)
Safety Issue:
Description:
Measure:Cohort E: Plasma concentration of ipatasertib at specified timepoints
Time Frame:Cycle 1, Day 1 and 15; Cycle 2, Day 1; Cycle 3, Day 15; Cycle 4, Day 1, and every even Cycle thereafter (one Cycle=28 days)
Safety Issue:
Description:
Measure:Cohort F: Serum concentration of trastuzumab emtansine at specified timepoints
Time Frame:Cycle 1, Day 1; Cycle 2, Day 1; Cycle 4, Day 1; Cycle 6, Day 1, and every even Cycle thereafter (one Cycle=21 days)
Safety Issue:
Description:
Measure:Cohort G: Plasma concentration of idasanutlin at specified timepoint
Time Frame:Cycle 1, Day 1, 2, 5, 8; Cycle 2, Day 1, 2, 5; Cycle 3, Day 2, 5; Cycle 4, Day 1, and every other Cycle going forward (one Cycle=28 days)
Safety Issue:
Description:
Measure:Cohort H: Plasma concentration of GDC-0077 at specified timepoints
Time Frame:Cycle 1, Day 1, 8 (+/-1 day), 15 (+/-1 day); Cycle 2, Day 1 (+/-1 day); Day 1 of Cycle 4, and every other even Cycle going forward (one Cycle=28 days)
Safety Issue:
Description:
Measure:Cohorts D, F: Percentage of participants with anti-drug antibodies (ADA)
Time Frame:Cohort D: Day 1 of Cycle 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, and every even Cycles thereafter (one Cycle=21 days); Cohort F: Cycle 1, Day 1; Cycle 2, Day 1; Cycle 4, Day 1; Cycle 6, Day 1, and every even Cycle thereafter (one Cycle=21 days)
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

October 11, 2020