Tumor-agnostic Precision Immuno-oncology and Somatic Targeting Rational for You (TAPISTRY) Platform Study

Tumor-agnostic Precision Immuno-oncology and Somatic Targeting Rational for You (TAPISTRY) Phase II Platform Trial

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: Trastuzumab emtansine; Drug: Inavolisib; Drug: Entrectinib; Drug: Entrectinib; Drug: Alectinib; Drug: Atezolizumab; Drug: Ipatasertib; Drug: Belvarafenib; Drug: Pralsetinib; Drug: Divarasib; Drug: Camonsertib

• Study Type: Interventional
• Enrollment (Estimated): 920
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Kinghorn Cancer Centre
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
    • Parkville, Victoria, Australia, 3052
      • Royal Children's Hospital
• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires St-Luc
  • Charleroi, Belgium, 6060
    • GHdC Site Les Viviers
  • Edegem, Belgium, 2650
    • UZ Antwerpen
  • Ghent, Belgium, 9000
    • UZ Gent
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
• Brazil
  • São Paulo
    • São Paulo, São Paulo, Brazil, 01509-010
      • Hospital A. C. Camargo
    • São Paulo, São Paulo, Brazil, 01308-050
      • Hospital Sírio-Libanês
    • São Paulo, São Paulo, Brazil, 04543-000
      • Clínica Onco Star - Rede D'Or
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1J3
      • BC Cancer ? Vancouver
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital - General Campus
    • Toronto, Ontario, Canada, M5G 1H3
      • The Hospital for Sick Children
• China
  • Beijing, China, 100142
    • Beijing Cancer Hospital
  • Beijing, China
    • Beijing Children's Hospital, Capital Medical University
  • Chengdu, China, 610047
    • West China Hospital - Sichuan University
  • Shanghai, China, 200092
    • Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
  • Shanghai, China
    • Zhongshan Hospital Fudan Unvierstiy
  • Tianjin, China, 300060
    • Tianjin Cancer Hospital
  • Xi'an, China, 710061
    • First Affiliated Hospital of Medical College of Xi'an Jiaotong University
• Denmark
  • København Ø, Denmark, 2100
    • Rigshospitalet
• France
  • Bordeaux, France, 33076
    • Institut Bergonié
  • Lille, France, 59020
    • Centre Oscar Lambret
  • Lyon, France, 69373
    • Centre Leon Berard
  • Marseille, France, 13005
    • Hopital de la Timone
  • Toulouse, France, 31059
    • Institut Universitaire du cancer de Toulouse-Oncopole
  • Villejuif, France, 94805
    • Institut de Cancerologie Gustave-Roussy (IGR)
• Germany
  • Essen, Germany, 45122
    • Uniklinik Essen
  • Göttingen, Germany, 37075
    • Georg-August-Uniklinik
  • Heilbronn, Germany, 74078
    • SLK-Kliniken Heilbronn GmbH;Klinik für Innere Medizin III
  • Mönchengladbach, Germany, 41066
    • Praxis für Hämatologie, Onkologie und Palliativmedizin
• Hong Kong
  • Hong Kong, Hong Kong
    • Hong Kong Children's Hospital
  • Shatin, Hong Kong
    • Prince of Wales Hospital
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus
  • Jerusalem, Israel, 9112001
    • Hadassah University Hospital - Ein Kerem
  • Petah Tikva, Israel, 4941492
    • Rabin MC
  • Ramat Gan, Israel, 5262100
    • Sheba Medical Center
  • Tel Aviv, Israel, 6423906
    • Sourasky / Ichilov Hospital
• Italy
  • Lazio
    • Rome, Lazio, Italy, 00165
      • Ospedale Pediatrico Bambino Gesù - IRCCS
    • Rome, Lazio, Italy, 00168
      • Policlinico Universitario Agostino Gemelli IRCCS
  • Lombardy
    • Brescia, Lombardy, Italy, 25100
      • Asst Degli Spedali Civili Di Brescia
    • Milan, Lombardy, Italy, 20133
      • Irccs Istituto Nazionale Dei Tumori (Int)
    • Milan, Lombardy, Italy, 20133
      • Istituto Nazionale Tumori di Milano
  • Piedmont
    • Turin, Piedmont, Italy, 10126
      • Dipartimento di Scienze Pediatriche Adolescenza
  • Tuscany
    • Siena, Tuscany, Italy, 53100
      • Azienda Ospedaliera Universitaria Senese, U.O.C. Immunoterapia Oncologica
• Japan
  • Osaka, Japan, 589-8511
    • Kindai University Hospital
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital, Cancer and Blood Research
• Poland
  • Gda?sk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii
  • Warsaw, Poland, 02-781
    • Narod.Inst.Onkol. im. M.Sklodowskiej - Curie-Panst.Inst.Bad
• Portugal
  • Porto, Portugal, 4200-072
    • IPO do Porto
• Puerto Rico
  • San Juan, Puerto Rico, 00935
    • PanOncology Trials
• Singapore
  • Singapore, Singapore, 119228
    • National University Hospital
  • Singapore, Singapore, 168583
    • National Cancer Centre
• South Korea
  • Gyeonggi-do, South Korea, 13620
    • Seoul National University Bundang Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, 03080
    • Seoul National University Hospital- Adult Site
  • Seoul, South Korea, 03080
    • Seoul National University Hospital- Pediatric Site
  • Seoul, South Korea, 06351
    • Samsung Medical Center- Adult Site
  • Seoul, South Korea, 06351
    • Samsung Medical Center- Pediatric Site
• Spain
  • Barcelona, Spain, 08035
    • Vall d?Hebron Institute of Oncology (VHIO), Barcelona
  • Barcelona, Spain, 08035
    • Vall d'Hebron Institute of Oncology (VHIO), Barcelona
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28009
    • Hospital Infantil Universitario Nino Jesus
  • Madrid, Spain, 28040
    • START Madrid-FJD, Hospital Fundacion Jimenez Diaz
  • Madrid, Spain, 28050
    • START Madrid. Centro Integral Oncologico Clara Campal
  • Madrid, Spain, 28027
    • Clinica Universidad de Navarra Madrid
  • Valencia, Spain, 46026
    • Hospital Universitario la Fe
  • Barcelona
    • Esplugues de Llobregas, Barcelona, Spain, 08950
      • Hospital Sant Joan de Déu
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital, Klinik und Poliklinik für Medizinische Onkologie
• Taiwan
  • Tainan, Taiwan, 00704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 112201
    • Taipei Veterans General Hospital
  • Taoyuan County, Taiwan, 333
    • Chang Gung Memorial Hospital-Linkou
  • Zhongzheng Dist., Taiwan, 10048
    • National Taiwan University Hospital
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Centre
  • London, United Kingdom, NW1 - 2PG
    • University College London Hospital
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
• United States
  • Arizona
    • Goodyear, Arizona, United States, 85338
      • Western Regional Medical Center at Cancer Treatment Centers of America
  • California
    • Los Angeles, California, United States, 90033
      • USC Norris Cancer Center
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Los Angeles
    • Newport Beach, California, United States, 92658
      • Hoag Memorial Hospital
    • Sacramento, California, United States, 95817
      • UC Davis Comprehensive Cancer Center
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer & Blood Center, LLC
  • Idaho
    • Boise, Idaho, United States, 83706
      • St. Alphonsus
  • Illinois
    • Zion, Illinois, United States, 60099
      • Midwestern Regional Med Center
  • Indiana
    • Lafayette, Indiana, United States, 47905
      • Horizon Oncology Research, Inc.
  • Maryland
    • Silver Spring, Maryland, United States, 20904
      • Maryland Hematology & Oncology. P.A.
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Minnesota
    • Saint Louis Park, Minnesota, United States, 55416
      • Metro-Minnesota Community Oncology Research Consortium
  • Montana
    • Billings, Montana, United States, 59102
      • Intermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Cancer Institute of New Jersey
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico
  • New York
    • New York, New York, United States, 10029
      • ICAHN School of Medicine at Mount Sinai
    • New York, New York, United States, 11101
      • Memorial Sloan Kettering Cancer Center
    • The Bronx, New York, United States, 10461
      • Montefiore Einstein Center for Cancer Care
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care Inc
    • Cincinnati, Ohio, United States, 45219
      • Barrett Cancer Center
  • Pennsylvania
    • Broomall, Pennsylvania, United States, 19008
      • Consultants in Medical Oncology and Hematology
    • Horsham, Pennsylvania, United States, 19044
      • Alliance Cancer Specialists
    • Leesburg, Pennsylvania, United States, 20176
      • Virginia Cancer Specialists - Leesburg
    • Philadelphia, Pennsylvania, United States, 19124
      • Cancer Treatment Centers of America
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • The West Clinic
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital
  • Texas
    • Austin, Texas, United States, 78731
      • Texas Oncology - Central South
    • Dallas, Texas, United States, 75246
      • Texas Oncology - Baylor Charles A. Sammons Cancer Center
    • Dallas, Texas, United States, 75230
      • Mary Crowley Medical Research Center
    • Houston, Texas, United States, 77030-4009
      • The University of Texas MD Anderson Cancer Center
    • Tyler, Texas, United States, 75702
      • Texas Oncology- Northeast Texas
  • Washington
    • Tacoma, Washington, United States, 98405
      • NorthWest Medical Specialties, PLLC
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert and the Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Entrectinib; Adults and pediatric participants with a BSA ≥1.51 m^2: entrectinib will be self-administered by participants orally at home at a dose of 600 mg/day (three 200-mg capsules per day). Pediatric participants with a BSA < 1.51 m^2: entrectinib will be administered orally at home in mini-tablet formulation at a dose of 400 mg/day (BSA=1.11-1.50 m^2) or 300 mg/day (BSA=0.81-1.10 m^2) or 200 mg/day (BSA=0.51-0.80 m^2) or 300 milligrams per square meter (mg/m^2) (BSA=0.43-0.50 m^2).; Other Names: Rozlytrek; Drug: Entrectinib; Adults and pediatric participants with a BSA ≥ 1.51 m^2: entrectinib will be self-administered by participants orally at home at a dose of 600 mg/day (three 200-mg capsules per day). Pediatric participants with a BSA < 1.51 m^2: entrectinib will be administered orally at home in mini-tablet formulation at a dose of 400 mg/day (BSA=1.11-1.50 m^2) or 300 mg/day (BSA=0.81-1.10 m^2) or 200 mg/day (BSA=0.51-0.80 m^2) or 300 mg/m^2 (BSA=≤0.50 m^2).; Other Names: Rozlytrek
Experimental: 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.	Drug: Entrectinib; Adults and pediatric participants with a BSA ≥1.51 m^2: entrectinib will be self-administered by participants orally at home at a dose of 600 mg/day (three 200-mg capsules per day). Pediatric participants with a BSA < 1.51 m^2: entrectinib will be administered orally at home in mini-tablet formulation at a dose of 400 mg/day (BSA=1.11-1.50 m^2) or 300 mg/day (BSA=0.81-1.10 m^2) or 200 mg/day (BSA=0.51-0.80 m^2) or 300 milligrams per square meter (mg/m^2) (BSA=0.43-0.50 m^2).; Other Names: Rozlytrek; Drug: Entrectinib; Adults and pediatric participants with a BSA ≥ 1.51 m^2: entrectinib will be self-administered by participants orally at home at a dose of 600 mg/day (three 200-mg capsules per day). Pediatric participants with a BSA < 1.51 m^2: entrectinib will be administered orally at home in mini-tablet formulation at a dose of 400 mg/day (BSA=1.11-1.50 m^2) or 300 mg/day (BSA=0.81-1.10 m^2) or 200 mg/day (BSA=0.51-0.80 m^2) or 300 mg/m^2 (BSA=≤0.50 m^2).; Other Names: Rozlytrek
Experimental: 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.	Drug: Alectinib; Alectinib will be administered orally BID with food at a dosage of 600 mg (four 150-mg capsules).; Other Names: Alecensa
Experimental: 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.	Drug: Trastuzumab emtansine; Trastuzumab emtansine will be administered at 3.6 mg/kg by IV infusion every 21 days until disease progression or unacceptable toxicity. The dosage and administration method also applies for pediatric participants 12-17 years of age.; Other Names: Kadcyla
Experimental: 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.	Drug: Inavolisib; GDC-077 will be administered QD at a starting dose of 9 mg PO in repeated 28-day cycles. The dosage and administration method also applies for pediatric participants 12-17 years of age.; Other Names: GDC-0077
Experimental: 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.	Drug: Belvarafenib; Belvarafenib will be administered at a dose 400 mg, 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.
Experimental: 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).	Drug: Divarasib; Divarasib will be self-administered by participants orally at home (except on clinic days) on a continuous daily dosing regimen for both adult and pediatric participants. A treatment cycle consists of 3 weeks (21 days).; Other Names: GDC-6036
Experimental: 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.	Drug: Atezolizumab; Atezolizumab will be administered by IV infusion at a fixed dose of 1200 mg 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.; Other Names: Tecentriq
Experimental: 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.	Drug: Ipatasertib; 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, beginning of Cycle 1, on Days 1-21 of each 28-day cycle until the participant experiences disease progression, intolerable toxicity, or withdraws consent.
Experimental: 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.	Drug: Belvarafenib; Belvarafenib will be administered at a dose 400 mg, 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.
Experimental: 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.	Drug: Pralsetinib; Pralsetinib will be self-administered by participants 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).; Other Names: Gavreto (US)
Experimental: 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.	Drug: Camonsertib; Camonsertib will be self-administered by participants orally at home (except on clinic days). A treatment cycle consists of 3 weeks and will be given on days 1-3 and days 8-10 of every 21-day cycle.
Experimental: 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.	Drug: Camonsertib; Camonsertib will be self-administered by participants orally at home (except on clinic days). A treatment cycle consists of 3 weeks and will be given on days 1-3 and days 8-10 of every 21-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Confirmed objective response indicates ≥4 weeks after initial documentation of response.	Approximately up to 12 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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: Overall Survival (OS)		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, 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: 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
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: IRC- and INV-assessed Time to Central Nervous System (CNS) Progression per RECIST v1.1		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, 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-PFS Rate 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
All Cohorts: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	AE severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5 (NCI CTCAE v5.0.)	Approximately up to 12 years
Cohorts A, B and F: 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)	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.	Approximately up to 12 years
Cohorts A, B and F: Change From Baseline in the EORTC-QLQ-C30 Total Score	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.	Approximately up to 12 years
Cohorts A, B and F: Percentage of Participants With a Clinical Meaningful Change on the Global Health Status, Physical Functioning, and Role Functioning Scores From the EORTC QLQ-C30	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.	Approximately up to 12 years
Cohorts A, B and F: Time to Confirmed Symptom Onset or Worsening From Tumor-related Symptom Scores From the EORTC QLQ-C30 and EORTC Item Library 71 (IL71)	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.	Approximately up to 12 years
Cohort F: Serum Concentration of Trastuzumab Emtansine at Specified Timepoints		Cycle 1, Day 1; Cycle 2, Day 1; Cycle 4, Day 1; Cycle 6, Day 1, and every even Cycle thereafter (up to approximately 25 months) (one Cycle=21 days)
Cohort F: Percentage of Participants with Anti-drug Antibodies (ADA)		Cycle 1, Day 1; Cycle 2, Day 1; Cycle 4, Day 1; Cycle 6, Day 1, and every even Cycle thereafter (up to approximately 25 months) (one Cycle=21 days)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

General Publications

• Desai AV, Bagchi A, Armstrong AE, van Tilburg CM, Basu EM, Robinson GW, Wang H, Casanova M, Andre N, Campbell-Hewson Q, Wu Y, Cardenas A, Ci B, Ryklansky C, Devlin CE, Meneses-Lorente G, Wulff J, Hutchinson KE, Gajjar A, Fox E. Efficacy and safety of entrectinib in children with extracranial solid or central nervous system (CNS) tumours harbouring NTRK or ROS1 fusions. Eur J Cancer. 2025 May 2;220:115308. doi: 10.1016/j.ejca.2025.115308. Epub 2025 Feb 22.
• Bagchi A, Chiang J, Pinto S, Dhanda S, Gajjar A. Infant-Type Hemispheric Gliomas: A Review of Clinical, Radiologic, Histopathologic, and Molecular Features. J Natl Compr Canc Netw. 2025 Nov;23(11):e257064. doi: 10.6004/jnccn.2025.7064.

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2021
• Primary Completion (Estimated): September 25, 2032
• Study Completion (Estimated): September 25, 2032

Study Registration Dates

• First Submitted: October 11, 2020
• First Submitted That Met QC Criteria: October 11, 2020
• First Posted (Actual): October 19, 2020

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Polycyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Macrolides; Lactones; Lactams, Macrocyclic; Macrocyclic Compounds; Maytansine; Trastuzumab; Ado-Trastuzumab Emtansine; ipatasertib; atezolizumab; entrectinib; inavolisib; alectinib; pralsetinib
• Other Study ID Numbers: BO41932; 2020-001847-16 (EudraCT Number); 2023-507418-28-00 (Ctis: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No