Recruiting
Phase 1

Targeted Therapies

Sponsor:

Hoffmann-La Roche

Code:

NCT04929223

Conditions

Metastatic Colorectal Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Inavolisib

Bevacizumab

Cetuximab

Atezolizumab

Tiragolumab

Study Details

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

Study ID

NCT04929223

Start date

Oct 22, 2021

Status verified date

Aug, 2026

Completion date

Aug 31, 2030

Anticipated

Primary completion date

Aug 31, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

542 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 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.

experimental: 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.

experimental: 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.

experimental: 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.

experimental: 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.

experimental: 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.

experimental: 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.

experimental: 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.

experimental: 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.

experimental: 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.

Interventions

Inavolisib

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

Bevacizumab

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

Cetuximab

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

Atezolizumab

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

Tiragolumab

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

SY-5609

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

Divarasib

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

FOLFOX

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

FOLFIRI

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

FoundationOne®Liquid CDx

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

Primary outcome measure

  • Objective Response Rate [ Time Frame: Approximately 84 months ]

Central Contacts and Locations

Central contacts

Reference Study ID Number: WO42758 https://forpatients.roche.com/ No attachments to email below.

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

Locations

Mayo Clinic Arizona

Recruiting

Phoenix, Arizona, United States, 85259

City of Hope Comprehensive Cancer Center

Recruiting

Duarte, California, United States, 91010

Cedars-Sinai Medical Center

Recruiting

Los Angeles, California, United States, 90048

UCLA

Recruiting

Los Angeles, California, United States, 90095

University of Colorado Cancer Center

Recruiting

Aurora, Colorado, United States, 80045

Rocky Mountain Cancer Centers, LLP

Recruiting

Lone Tree, Colorado, United States, 80124

Yale Cancer Center

Recruiting

New Haven, Connecticut, United States, 06520

Mayo Clinic in Florida

Recruiting

Jacksonville, Florida, United States, 32224

Moffitt Cancer Center

Recruiting

Tampa, Florida, United States, 33612

Illinois Cancer Specialists

Recruiting

Arlington Heights, Illinois, United States, 60005

Mary Bird Perkins Cancer Ctr

Recruiting

Baton Rouge, Louisiana, United States, 70809

Mayo Clinic Rochester

Recruiting

Rochester, Minnesota, United States, 55902

New York Cancer & Blood Specialists - New Hyde Park

Recruiting

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

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

Recruiting

New York, New York, United States, 10028

New York Cancer & Blood Specialists

Recruiting

Port Jefferson Station, New York, United States, 11776

New York Cancer & Blood Specialists - Bronx

Recruiting

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

Hematology Oncology Salem

Recruiting

Salem, Oregon, United States, 97301

SCRI Oncology Partners

Recruiting

Nashville, Tennessee, United States, 37203

Texas Oncology - Northeast Texas

Recruiting

Denton, Texas, United States, 76201

Texas Oncology - Gulf Coast

Recruiting

Webster, Texas, United States, 77598-4420

More Information

Sponsor

Hoffmann-La Roche

Last update posted

Aug 17, 2026

Last verified

Aug, 2026

Keywords

  • KRAS G12C

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Hoffmann-La Roche on 2026-08-17.