A Study Evaluating the Safety and Efficacy of Targeted Therapies in Subpopulations of Patients With Metastatic Colorectal Cancer (INTRINSIC)

NCT ID: NCT04929223

Last Updated: 2025-11-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

542 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-10-22

Study Completion Date

2028-11-07

Brief Summary

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This open-label, exploratory study is designed to evaluate the safety and efficacy of targeted therapies or immunotherapy as single agents or combinations, in participants with metastatic colorectal cancer (mCRC) whose tumors are biomarker positive as per treatment arm-specific definition. Eligible participants with mCRC will be enrolled into specific treatment arms based on their biomarker assay results.

Detailed Description

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Conditions

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Metastatic Colorectal Cancer

Keywords

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KRAS G12C

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Inavolisib + Cetuximab

Participants will receive 9 milligrams (mg) of inavolisib by mouth once daily (QD) on Days 8-28 of Cycle 1, then QD on Days 1-28 from Cycle 2 onwards (1 cycle=28 days).

Participants will also receive cetuximab intravenous (IV) infusion 400 mg/m2 body surface area on Day 1 of Cycle 1. All subsequent weekly (QW) doses will be 250 mg/m2 each. This arm is closed.

Group Type EXPERIMENTAL

Inavolisib

Intervention Type DRUG

Inavolisib will be administered orally as per schedule specified in the respective arms.

Cetuximab

Intervention Type DRUG

Cetuximab IV will be administered as per schedule specified in the respective arm.

FoundationOne®Liquid CDx

Intervention Type DIAGNOSTIC_TEST

FoundationOne®Liquid CDx is used to identify presence of genomic alterations for participant cohort assignment.

Inavolisib + Bevacizumab

Participants will receive 9 mg of inavolisib by mouth QD combined with bevacizumab 15 milligram/kilogram (mg/kg) IV once every three weeks (Q3W) on Day 1 of each cycle (1 cycle=21 days). This arm is closed.

Group Type EXPERIMENTAL

Inavolisib

Intervention Type DRUG

Inavolisib will be administered orally as per schedule specified in the respective arms.

Bevacizumab

Intervention Type DRUG

Bevacizumab IV will be administered as per schedule specified in the respective arm.

FoundationOne®Liquid CDx

Intervention Type DIAGNOSTIC_TEST

FoundationOne®Liquid CDx is used to identify presence of genomic alterations for participant cohort assignment.

Atezolizumab + Tiragolumab + Bevacizumab

Participants in this randomized cohort will receive 1200 mg of atezolizumab by IV infusion on Day 1 of each cycle, combined with tiragolumab at a dose of 600 mg IV infusion on Day 1 of each cycle and bevacizumab IV infusion at a dose of 15 mg/kg on Day 1 of each cycle. (Cycle length=21 days) This arm is active, and not recruiting participants.

Group Type EXPERIMENTAL

Bevacizumab

Intervention Type DRUG

Bevacizumab IV will be administered as per schedule specified in the respective arm.

Atezolizumab

Intervention Type DRUG

Atezolizumab IV infusion will be administered as per schedule specified in the respective arm.

Tiragolumab

Intervention Type DRUG

Tiragolumab IV infusion will be administered as per schedule specified in the respective arm.

FoundationOne®Liquid CDx

Intervention Type DIAGNOSTIC_TEST

FoundationOne®Liquid CDx is used to identify presence of genomic alterations for participant cohort assignment.

Atezolizumab + Tiragolumab

Participants in this randomized cohort will receive 1200 mg of atezolizumab by IV infusion on Day 1 of each cycle combined with tiragolumab 600 mg IV infusion on Day 1 of each cycle. (Cycle length=21 days) This arm is active, and not recruiting participants.

Group Type EXPERIMENTAL

Atezolizumab

Intervention Type DRUG

Atezolizumab IV infusion will be administered as per schedule specified in the respective arm.

Tiragolumab

Intervention Type DRUG

Tiragolumab IV infusion will be administered as per schedule specified in the respective arm.

FoundationOne®Liquid CDx

Intervention Type DIAGNOSTIC_TEST

FoundationOne®Liquid CDx is used to identify presence of genomic alterations for participant cohort assignment.

Atezolizumab + SY-5609

Participants will receive 1680 mg of atezolizumab by IV infusion on Day 1 of each cycle Q4W in repeated 28-day cycles combined with SY-5609 at a dose of 3, 4, 5, 6, 7 or 10 mg by mouth for 7 days, followed by 7 days off. (Cycle length=28 days) This arm is closed.

Group Type EXPERIMENTAL

Atezolizumab

Intervention Type DRUG

Atezolizumab IV infusion will be administered as per schedule specified in the respective arm.

SY-5609

Intervention Type DRUG

SY-5609 will be administered by mouth as per schedule specified in the respective arm.

FoundationOne®Liquid CDx

Intervention Type DIAGNOSTIC_TEST

FoundationOne®Liquid CDx is used to identify presence of genomic alterations for participant cohort assignment.

Divarasib + Cetuximab + FOLFOX

Participants will receive cetuximab IV 500 mg/m2 body surface area on Days 1 and 15 and FOLFOX on Days 1 and 15 with divarasib PO QD on Days 1-28. (Cycle length=28 days) This arm is recruiting participants.

Group Type EXPERIMENTAL

Cetuximab

Intervention Type DRUG

Cetuximab IV will be administered as per schedule specified in the respective arm.

Divarasib

Intervention Type DRUG

Divarasib will be administered orally as per schedule specified in the respective arms.

FOLFOX

Intervention Type DRUG

FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) IV will be administered as per schedule specified in the respective arm.

FoundationOne®Liquid CDx

Intervention Type DIAGNOSTIC_TEST

FoundationOne®Liquid CDx is used to identify presence of genomic alterations for participant cohort assignment.

Divarasib + Cetuximab

Participants will receive cetuximab IV 500 mg/m2 body surface area on Days 1 and 15 with divarasib PO QD on Days 1-28. (Cycle length=28 days) This arm is active, and not recruiting participants.

Group Type EXPERIMENTAL

Cetuximab

Intervention Type DRUG

Cetuximab IV will be administered as per schedule specified in the respective arm.

Divarasib

Intervention Type DRUG

Divarasib will be administered orally as per schedule specified in the respective arms.

FoundationOne®Liquid CDx

Intervention Type DIAGNOSTIC_TEST

FoundationOne®Liquid CDx is used to identify presence of genomic alterations for participant cohort assignment.

Divarasib + Cetuximab + FOLFIRI

Participants will receive cetuximab IV 500 mg/m2 body surface area on Days 1 and 15 and FOLFIRI on Days 1 and 15 with divarasib PO QD on Days 1-28. (Cycle length=28 days) This arm is active, and not recruiting participants.

Group Type EXPERIMENTAL

Cetuximab

Intervention Type DRUG

Cetuximab IV will be administered as per schedule specified in the respective arm.

Divarasib

Intervention Type DRUG

Divarasib will be administered orally as per schedule specified in the respective arms.

FOLFIRI

Intervention Type DRUG

FOLFIRI (leucovorin, 5-fluorouracil, irinotecan) IV will be administered as per schedule specified in the respective arm.

FoundationOne®Liquid CDx

Intervention Type DIAGNOSTIC_TEST

FoundationOne®Liquid CDx is used to identify presence of genomic alterations for participant cohort assignment.

Divarasib + Bevacizumab + FOLFOX

Participants will receive Bevacizumab 5 mg/kg by IV infusion on Days 1 and 15 and FOLFOX on Days 1 and 15 with Divarasib PO QD on Days 1-28. (Cycle length=28 days) This arm is recruiting participants.

Group Type EXPERIMENTAL

Bevacizumab

Intervention Type DRUG

Bevacizumab IV will be administered as per schedule specified in the respective arm.

Divarasib

Intervention Type DRUG

Divarasib will be administered orally as per schedule specified in the respective arms.

FOLFOX

Intervention Type DRUG

FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) IV will be administered as per schedule specified in the respective arm.

FoundationOne®Liquid CDx

Intervention Type DIAGNOSTIC_TEST

FoundationOne®Liquid CDx is used to identify presence of genomic alterations for participant cohort assignment.

Divarasib + Bevacizumab + FOLFIRI

Participants will receive Bevacizumab 5 mg/kg by IV infusion on Days 1 and 15 and FOLFIRI on Days 1 and 15 with Divarasib PO QD on Days 1-28. (Cycle length=28 days) This arm is recruiting participants.

Group Type EXPERIMENTAL

Bevacizumab

Intervention Type DRUG

Bevacizumab IV will be administered as per schedule specified in the respective arm.

Divarasib

Intervention Type DRUG

Divarasib will be administered orally as per schedule specified in the respective arms.

FOLFIRI

Intervention Type DRUG

FOLFIRI (leucovorin, 5-fluorouracil, irinotecan) IV will be administered as per schedule specified in the respective arm.

FoundationOne®Liquid CDx

Intervention Type DIAGNOSTIC_TEST

FoundationOne®Liquid CDx is used to identify presence of genomic alterations for participant cohort assignment.

Interventions

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Inavolisib

Inavolisib will be administered orally as per schedule specified in the respective arms.

Intervention Type DRUG

Bevacizumab

Bevacizumab IV will be administered as per schedule specified in the respective arm.

Intervention Type DRUG

Cetuximab

Cetuximab IV will be administered as per schedule specified in the respective arm.

Intervention Type DRUG

Atezolizumab

Atezolizumab IV infusion will be administered as per schedule specified in the respective arm.

Intervention Type DRUG

Tiragolumab

Tiragolumab IV infusion will be administered as per schedule specified in the respective arm.

Intervention Type DRUG

SY-5609

SY-5609 will be administered by mouth as per schedule specified in the respective arm.

Intervention Type DRUG

Divarasib

Divarasib will be administered orally as per schedule specified in the respective arms.

Intervention Type DRUG

FOLFOX

FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) IV will be administered as per schedule specified in the respective arm.

Intervention Type DRUG

FOLFIRI

FOLFIRI (leucovorin, 5-fluorouracil, irinotecan) IV will be administered as per schedule specified in the respective arm.

Intervention Type DRUG

FoundationOne®Liquid CDx

FoundationOne®Liquid CDx is used to identify presence of genomic alterations for participant cohort assignment.

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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Avastin Tecentriq GDC-6036

Eligibility Criteria

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Inclusion Criteria

* Signed cohort-specific Informed Consent Form
* Age \>= 18 years at time of signing Informed Consent Form
* Biomarker eligibility as determined by:

* A validated test approved by local health authorities for detection of the specified biomarkers/mutations.
* A validated test performed at a College of American Pathologists/clinical laboratory improvement amendments (CAP/CLIA) -certified or equivalently accredited diagnostic laboratory using a validated test for detection of the specified biomarkers.
* Prior test results completed before signing cohort-specific Informed Consent Form or local test results generated prior to or during screening, and availability of a full report of the testing results OR
* Blood-based FoundationOne Liquid CDx biomarker eligibility test result generated prior to or during screening or, in case of re-enrollment after treatment discontinuation, prior to starting a new anti-cancer therapy.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of \<= 1
* Life expectancy \>= 3 months, as determined by the investigator
* Histologically confirmed adenocarcinoma originating from the colon or rectum
* Metastatic disease
* Prior therapies for metastatic disease
* Ability to comply with the study protocol, in the investigators judgment
* Measurable disease (at least one target lesion) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
* Baseline tumor tissue samples will be collected from all participants for exploratory biomarker research
* Adequate hematologic and organ function within 14 days prior to initiation of study treatment
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures
* For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm

Exclusion Criteria

* Current participation or enrollment in another interventional clinical trial. Participants who are participating in the follow-up period of an interventional clinical trial are eligible for the study.
* Any systemic anti-cancer treatment within 2 weeks or 5 half-lives (whichever is shorter) prior to start of study treatment
* Treatment with investigational therapy within 28 days prior to initiation 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 patient's safe participation in and completion of the study or confounds the ability to interpret data from the study
* Severe infection within 4 weeks prior to initiation of study treatment or any active infection that, in the opinion of the investigator, could impact patient safety
* 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
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
* Uncontrolled tumor-related pain
* Uncontrolled or symptomatic hypercalcemia
* Clinically significant and active liver disease
* Negative HIV test at screening, with the following exception: Participants with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy for at least 4 weeks, have a CD4 count greater than or equal to 200/uL, have an undetectable viral load, and have not had a history of opportunistic infection attributable to AIDS within the last 12 months.
* Symptomatic, untreated, or actively progressing CNS metastases
* History of leptomeningeal disease or carcinomatous meningitis
* History of malignancy other than CRC within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
* Any other disease, unresolved toxicity from prior therapy, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the participant at high risk from treatment complications
* Requirement for treatment with any medicinal product that contraindicates the use of any of the study treatments, may interfere with the planned treatment, affects participant compliance, or puts the patient at higher risk for treatment-related complications
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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UAB Comprehensive Cancer Center

Birmingham, Alabama, United States

Site Status WITHDRAWN

Mayo Clinic Arizona

Phoenix, Arizona, United States

Site Status COMPLETED

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status ACTIVE_NOT_RECRUITING

cCare

Encinitas, California, United States

Site Status WITHDRAWN

USC Norris Cancer Center

Los Angeles, California, United States

Site Status RECRUITING

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status ACTIVE_NOT_RECRUITING

UCLA

Los Angeles, California, United States

Site Status RECRUITING

Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States

Site Status WITHDRAWN

Stanford Cancer Center

Stanford, California, United States

Site Status COMPLETED

University of Colorado Cancer Center

Aurora, Colorado, United States

Site Status ACTIVE_NOT_RECRUITING

Yale Cancer Center

New Haven, Connecticut, United States

Site Status RECRUITING

Eastern Ct Hema/Onco Assoc

Norwich, Connecticut, United States

Site Status RECRUITING

Mayo Clinic in Florida

Jacksonville, Florida, United States

Site Status ACTIVE_NOT_RECRUITING

Moffitt Cancer Center

Tampa, Florida, United States

Site Status ACTIVE_NOT_RECRUITING

Mary Bird Perkins Cancer Ctr

Baton Rouge, Louisiana, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status ACTIVE_NOT_RECRUITING

Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status WITHDRAWN

Mayo Clinic Rochester

Rochester, Minnesota, United States

Site Status RECRUITING

New York Cancer & Blood Specialists - New Hyde Park

New Hyde Park, New York, United States

Site Status RECRUITING

New York Cancer and Blood Specialists-Central Park Hematology & Oncology

New York, New York, United States

Site Status RECRUITING

New York Cancer & Blood Specialists

Port Jefferson Station, New York, United States

Site Status RECRUITING

New York Cancer & Blood Specialists - Bronx

The Bronx, New York, United States

Site Status RECRUITING

Duke University Medical Center

Durham, North Carolina, United States

Site Status COMPLETED

Hematology Oncology Salem

Salem, Oregon, United States

Site Status ACTIVE_NOT_RECRUITING

UPMC - Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status ACTIVE_NOT_RECRUITING

Sarah Cannon Research Institute / Tennessee Oncology

Nashville, Tennessee, United States

Site Status COMPLETED

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status COMPLETED

Lumi Research

Kingwood, Texas, United States

Site Status WITHDRAWN

Swedish Cancer Inst.

Seattle, Washington, United States

Site Status COMPLETED

Medical Oncology Associates

Spokane, Washington, United States

Site Status WITHDRAWN

Peter Maccallum Cancer Centre

Melbourne, Victoria, Australia

Site Status RECRUITING

Princess Margaret Cancer Center

Toronto, Ontario, Canada

Site Status ACTIVE_NOT_RECRUITING

Jewish General Hospital

Montreal, Quebec, Canada

Site Status WITHDRAWN

McGill University Health Center

Montreal, Quebec, Canada

Site Status WITHDRAWN

Rigshospitalet, Onkologisk Klinik

København Ø, , Denmark

Site Status RECRUITING

Charité Universitätsmedizin Berlin

Berlin, , Germany

Site Status RECRUITING

Katholisches Klinikum Bochum gGmbH - St. Josef-Hospital

Bochum, , Germany

Site Status RECRUITING

Universitätsklinik Carl Gustav Carus der Technischen Universität Dresden

Dresden, , Germany

Site Status RECRUITING

Universitätsklinikum Düsseldorf

Düsseldorf, , Germany

Site Status RECRUITING

Asklepios Klinik Altona

Hamburg, , Germany

Site Status RECRUITING

SLK-Kliniken Heilbronn GmbH;Klinik für Innere Medizin III

Heilbronn, , Germany

Site Status RECRUITING

Klinikum der Universität München, Campus Großhadern

München, , Germany

Site Status ACTIVE_NOT_RECRUITING

Universitätsklinikum Ulm

Ulm, , Germany

Site Status RECRUITING

Università degli Studi della Campania Luigi Vanvitelli

Napoli, Campania, Italy

Site Status RECRUITING

Policlinico Universitario Agostino Gemelli IRCCS

Rome, Lazio, Italy

Site Status RECRUITING

Irccs Istituto Nazionale Dei Tumori (Int)

Milan, Lombardy, Italy

Site Status RECRUITING

Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda)

Milan, Lombardy, Italy

Site Status RECRUITING

IRCCS Istituto Oncologico Veneto (IOV)

Padua, Veneto, Italy

Site Status RECRUITING

Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii

Krakow, , Poland

Site Status SUSPENDED

Uniwersytecki Szpital Kliniczny w Poznaniu

Poznan, , Poland

Site Status RECRUITING

Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie

Warsaw, , Poland

Site Status SUSPENDED

National Cancer Center

Goyang-si, , South Korea

Site Status RECRUITING

Chonnam National University Hwasun Hospital

Jeollanam-do, , South Korea

Site Status RECRUITING

Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Site Status RECRUITING

Samsung Medical Center

Seoul, , South Korea

Site Status RECRUITING

Seoul National University Hospital

Seoul, , South Korea

Site Status RECRUITING

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Site Status RECRUITING

Asan Medical Center

Seoul, , South Korea

Site Status RECRUITING

Vall d?Hebron Institute of Oncology (VHIO), Barcelona

Barcelona, , Spain

Site Status RECRUITING

START Madrid-FJD, Hospital Fundacion Jimenez Diaz

Madrid, , Spain

Site Status RECRUITING

START Madrid. Centro Integral Oncologico Clara Campal

Madrid, , Spain

Site Status WITHDRAWN

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Site Status RECRUITING

National Cheng Kung University Hospital

Tainan City, , Taiwan

Site Status RECRUITING

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status RECRUITING

National Taiwan University Hospital

Zhongzheng Dist., , Taiwan

Site Status RECRUITING

Addenbrookes Hospital

Cambridge, , United Kingdom

Site Status RECRUITING

Velindre Cancer Centre

Cardiff, , United Kingdom

Site Status RECRUITING

Royal Free Hospital

London, , United Kingdom

Site Status RECRUITING

Royal Marsden Hospital;Dept of Med-Onc

London, , United Kingdom

Site Status RECRUITING

Sarah Cannon Research Institute

London, , United Kingdom

Site Status ACTIVE_NOT_RECRUITING

Imperial College Healthcare NHS Trust

London, , United Kingdom

Site Status ACTIVE_NOT_RECRUITING

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Site Status RECRUITING

Royal Marsden Hospital

Sutton, , United Kingdom

Site Status RECRUITING

Countries

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France United States Australia Canada Denmark Germany Italy Poland South Korea Spain Taiwan United Kingdom

Central Contacts

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Reference Study ID Number: WO42758 https://forpatients.roche.com/

Role: CONTACT

Phone: 888-662-6728 (U.S. and Canada)

Email: [email protected]

Other Identifiers

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2021-001207-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-505163-37-00

Identifier Type: OTHER

Identifier Source: secondary_id

WO42758

Identifier Type: -

Identifier Source: org_study_id