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

NCT04929223 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: WO427582021-001207-332023-505163-37-00
• Study Type: interventional
• Target: 542
• Locations: 11 countries
• Sites: 82

Brief Summary

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.

Conditions

Metastatic Colorectal Cancer

Keywords

KRAS G12C

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Defined as the proportion of participants with a complete response or partial response, as determined by the investigator according to RECIST v1.1

  Approximately 84 months

Secondary Outcomes (6)

• Duration of Response

  Approximately 84 months

• Disease Control Rate

  Approximately 84 months

• Percentage of Participants with Adverse Events (AEs)

  Approximately 84 months

• Plasma Concentrations of Divarasib

  At pre-defined intervals from first administration of study drug up to approximately 84 months

• Recommended Dose of Divarasib in Combination with Bevacizumab and FOLFOX

  Approximately 84 months

Study Arms (10)

Inavolisib + Cetuximab

EXPERIMENTAL

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.

Drug: Inavolisib; Drug: Cetuximab; Diagnostic Test: FoundationOne®Liquid CDx

Inavolisib + Bevacizumab

EXPERIMENTAL

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.

Drug: Inavolisib; Drug: Bevacizumab; Diagnostic Test: FoundationOne®Liquid CDx

Atezolizumab + Tiragolumab + Bevacizumab

EXPERIMENTAL

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.

Drug: Bevacizumab; Drug: Atezolizumab; Drug: Tiragolumab; Diagnostic Test: FoundationOne®Liquid CDx

Atezolizumab + Tiragolumab

EXPERIMENTAL

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.

Drug: Atezolizumab; Drug: Tiragolumab; Diagnostic Test: FoundationOne®Liquid CDx

Atezolizumab + SY-5609

EXPERIMENTAL

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.

Drug: Atezolizumab; Drug: SY-5609; Diagnostic Test: FoundationOne®Liquid CDx

Divarasib + Cetuximab + FOLFOX

EXPERIMENTAL

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.

Drug: Cetuximab; Drug: Divarasib; Drug: FOLFOX; Diagnostic Test: FoundationOne®Liquid CDx

Divarasib + Cetuximab

EXPERIMENTAL

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.

Drug: Cetuximab; Drug: Divarasib; Diagnostic Test: FoundationOne®Liquid CDx

Divarasib + Cetuximab + FOLFIRI

EXPERIMENTAL

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.

Drug: Cetuximab; Drug: Divarasib; Drug: FOLFIRI; Diagnostic Test: FoundationOne®Liquid CDx

Divarasib + Bevacizumab + FOLFOX

EXPERIMENTAL

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.

Drug: Bevacizumab; Drug: Divarasib; Drug: FOLFOX; Diagnostic Test: FoundationOne®Liquid CDx

Divarasib + Bevacizumab + FOLFIRI

EXPERIMENTAL

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.

Drug: Bevacizumab; Drug: Divarasib; Drug: FOLFIRI; Diagnostic Test: FoundationOne®Liquid CDx

Interventions

Inavolisib DRUG

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

Inavolisib + Bevacizumab; Inavolisib + Cetuximab

Bevacizumab DRUG

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

Also known as: Avastin

Atezolizumab + Tiragolumab + Bevacizumab; Divarasib + Bevacizumab + FOLFIRI; Divarasib + Bevacizumab + FOLFOX; Inavolisib + Bevacizumab

Cetuximab DRUG

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

Divarasib + Cetuximab; Divarasib + Cetuximab + FOLFIRI; Divarasib + Cetuximab + FOLFOX; Inavolisib + Cetuximab

Atezolizumab DRUG

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

Also known as: Tecentriq

Atezolizumab + SY-5609; Atezolizumab + Tiragolumab; Atezolizumab + Tiragolumab + Bevacizumab

Tiragolumab DRUG

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

Atezolizumab + Tiragolumab; Atezolizumab + Tiragolumab + Bevacizumab

SY-5609 DRUG

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

Atezolizumab + SY-5609

Divarasib DRUG

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

Also known as: GDC-6036

Divarasib + Bevacizumab + FOLFIRI; Divarasib + Bevacizumab + FOLFOX; Divarasib + Cetuximab; Divarasib + Cetuximab + FOLFIRI; Divarasib + Cetuximab + FOLFOX

FOLFOX DRUG

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

Divarasib + Bevacizumab + FOLFOX; Divarasib + Cetuximab + FOLFOX

FOLFIRI DRUG

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

Divarasib + Bevacizumab + FOLFIRI; Divarasib + Cetuximab + FOLFIRI

FoundationOne®Liquid CDx DIAGNOSTIC_TEST

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

Atezolizumab + SY-5609; Atezolizumab + Tiragolumab; Atezolizumab + Tiragolumab + Bevacizumab; Divarasib + Bevacizumab + FOLFIRI; Divarasib + Bevacizumab + FOLFOX; Divarasib + Cetuximab; Divarasib + Cetuximab + FOLFIRI; Divarasib + Cetuximab + FOLFOX; Inavolisib + Bevacizumab; Inavolisib + Cetuximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (82)

UAB Comprehensive Cancer Center

Birmingham, Alabama, 35233, United States

WITHDRAWN

Mayo Clinic Arizona

Phoenix, Arizona, 85259, United States

COMPLETED

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

ACTIVE NOT RECRUITING

cCare

Encinitas, California, 92024, United States

WITHDRAWN

USC Norris Cancer Center

Los Angeles, California, 90033, United States

COMPLETED

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

ACTIVE NOT RECRUITING

UCLA

Los Angeles, California, 90095, United States

RECRUITING

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

WITHDRAWN

Stanford Cancer Center

Stanford, California, 94305-5820, United States

COMPLETED

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

ACTIVE NOT RECRUITING

Rocky Mountain Cancer Centers, LLP

Lone Tree, Colorado, 80124, United States

RECRUITING

Yale Cancer Center

New Haven, Connecticut, 06520, United States

RECRUITING

Eastern Ct Hema/Onco Assoc

Norwich, Connecticut, 06360, United States

WITHDRAWN

Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States

WITHDRAWN

Moffitt Cancer Center

Tampa, Florida, 33612, United States

ACTIVE NOT RECRUITING

Illinois Cancer Specialists

Arlington Heights, Illinois, 60005, United States

RECRUITING

Mary Bird Perkins Cancer Ctr

Baton Rouge, Louisiana, 70809, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114-2621, United States

COMPLETED

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

WITHDRAWN

Mayo Clinic Rochester

Rochester, Minnesota, 55902, United States

RECRUITING

New York Cancer & Blood Specialists - New Hyde Park

New Hyde Park, New York, 11042-1116, United States

RECRUITING

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

New York, New York, 10028, United States

RECRUITING

New York Cancer & Blood Specialists

Port Jefferson Station, New York, 11776, United States

RECRUITING

New York Cancer & Blood Specialists - Bronx

The Bronx, New York, 10469-5930, United States

RECRUITING

Duke University Medical Center

Durham, North Carolina, 27710, United States

COMPLETED

Hematology Oncology Salem

Salem, Oregon, 97301, United States

ACTIVE NOT RECRUITING

UPMC - Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

ACTIVE NOT RECRUITING

Sarah Cannon Research Institute / Tennessee Oncology

Nashville, Tennessee, 37203, United States

COMPLETED

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

COMPLETED

Texas Oncology - Northeast Texas

Denton, Texas, 76201, United States

RECRUITING

Lumi Research

Kingwood, Texas, 77339, United States

WITHDRAWN

Texas Oncology - Gulf Coast

Webster, Texas, 77598-4420, United States

RECRUITING

Swedish Cancer Inst.

Seattle, Washington, 98104, United States

COMPLETED

Medical Oncology Associates

Spokane, Washington, 99208, United States

WITHDRAWN

Peter Maccallum Cancer Centre

Melbourne, Victoria, 3000, Australia

RECRUITING

Princess Margaret Cancer Center

Toronto, Ontario, M5G 1X6, Canada

ACTIVE NOT RECRUITING

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

WITHDRAWN

McGill University Health Center

Montreal, Quebec, H4A 3J1, Canada

WITHDRAWN

Rigshospitalet, Onkologisk Klinik

København Ø, 2100, Denmark

RECRUITING

Charité Universitätsmedizin Berlin

Berlin, 13353, Germany

RECRUITING

Katholisches Klinikum Bochum gGmbH - St. Josef-Hospital

Bochum, 44791, Germany

RECRUITING

Universitätsklinik Carl Gustav Carus der Technischen Universität Dresden

Dresden, 01307, Germany

RECRUITING

Universitätsklinikum Düsseldorf

Düsseldorf, 40225, Germany

RECRUITING

Asklepios Klinik Altona

Hamburg, 22763, Germany

RECRUITING

SLK-Kliniken Heilbronn GmbH;Klinik für Innere Medizin III

Heilbronn, 74078, Germany

RECRUITING

Klinikum der Universität München, Campus Großhadern

München, 81377, Germany

WITHDRAWN

Universitätsklinikum Ulm

Ulm, 89081, Germany

RECRUITING

Università degli Studi della Campania Luigi Vanvitelli

Naples, Campania, 80131, Italy

RECRUITING

Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST - PPDS

Meldola, Emilia-Romagna, 47014, Italy

RECRUITING

Policlinico Universitario Agostino Gemelli IRCCS

Rome, Lazio, 00168, Italy

RECRUITING

Irccs Istituto Nazionale Dei Tumori (Int)

Milan, Lombardy, 20133, Italy

RECRUITING

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

Milan, Lombardy, 20162, Italy

RECRUITING

IRCCS Istituto Oncologico Veneto (IOV)

Padova, Veneto, 35128, Italy

RECRUITING

Uniwersyteckie Centrum Kliniczne, O?rodek Bada? Klinicznych Wczesnych Faz

Gdansk, 80-952, Poland

RECRUITING

Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii

Krakow, 30-688, Poland

SUSPENDED

Uniwersytecki Szpital Kliniczny w Poznaniu

Poznan, 60-569, Poland

RECRUITING

Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie

Warsaw, 02-781, Poland

SUSPENDED

National Cancer Center

Goyang-si, 10408, South Korea

RECRUITING

Chonnam National University Hwasun Hospital

Jeollanam-do, 58128, South Korea

RECRUITING

Seoul National University Bundang Hospital

Seongnam-si, 13605, South Korea

RECRUITING

Samsung Medical Center

Seoul, (0)6351, South Korea

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

Hospital Universitario Puerta de Hierro - Majadahonda

Majadahonda, Madrid, 28222, Spain

RECRUITING

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

Barcelona, 08035, Spain

RECRUITING

START Madrid-FJD, Hospital Fundacion Jimenez Diaz

Madrid, 28040, Spain

RECRUITING

START Madrid. Centro Integral Oncologico Clara Campal

Madrid, 28050, Spain

WITHDRAWN

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

RECRUITING

Hospital Clinico Universitario Lozano Blesa

Zaragoza, 50009, Spain

RECRUITING

National Cheng Kung University Hospital

Tainan, 00704, Taiwan

RECRUITING

Taipei Veterans General Hospital

Taipei, 112201, Taiwan

RECRUITING

National Taiwan University Hospital

Zhongzheng Dist., 10048, Taiwan

RECRUITING

Addenbrookes Hospital

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

Velindre Cancer Centre

Cardiff, CF14 2TL, United Kingdom

RECRUITING

Royal Free Hospital

London, NW3 2QG, United Kingdom

WITHDRAWN

Royal Marsden Hospital;Dept of Med-Onc

London, SW3 6JJ, United Kingdom

RECRUITING

Sarah Cannon Research Institute

London, W1G 6AD, United Kingdom

RECRUITING

Imperial College Healthcare NHS Trust

London, W2 1NY, United Kingdom

RECRUITING

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

RECRUITING

Royal Marsden Hospital

Sutton, SM2 5PT, United Kingdom

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

inavolisib; Bevacizumab; Cetuximab; atezolizumab; Tiragolumab; SY-5609; Folfox protocol; IFL protocol

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Central Study Contacts

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

CONTACT

888-662-6728 (U.S. and Canada); global-roche-genentech-trials@gene.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2021
• First Posted: June 18, 2021
• Study Start: October 22, 2021
• Primary Completion (Estimated): August 31, 2030
• Study Completion (Estimated): August 31, 2030
• Last Updated: May 26, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

KR (7); DK (1); PL (4); ES (6); TW (3); US (35); IT (6); CA (3); AU (1); DE (8); GB (8)