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Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

Phase
Phase 1
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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.
  • Drug: Inavolisib
    Inavolisib will be administered orally as per schedule specified in the respective arms.
  • Drug: Cetuximab
    Cetuximab IV will be administered as per schedule specified in the respective arm.
  • Diagnostic Test: FoundationOne®Liquid CDx
    FoundationOne®Liquid CDx is used to identify presence of genomic alterations for participant cohort assignment.
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.
  • Drug: Inavolisib
    Inavolisib will be administered orally as per schedule specified in the respective arms.
  • Drug: Bevacizumab
    Bevacizumab IV will be administered as per schedule specified in the respective arm.
    Other names:
    • Avastin
  • Diagnostic Test: FoundationOne®Liquid CDx
    FoundationOne®Liquid CDx is used to identify presence of genomic alterations for participant cohort assignment.
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.
  • Drug: Bevacizumab
    Bevacizumab IV will be administered as per schedule specified in the respective arm.
    Other names:
    • Avastin
  • Drug: Atezolizumab
    Atezolizumab IV infusion will be administered as per schedule specified in the respective arm.
    Other names:
    • Tecentriq
  • Drug: Tiragolumab
    Tiragolumab IV infusion will be administered as per schedule specified in the respective arm.
  • Diagnostic Test: FoundationOne®Liquid CDx
    FoundationOne®Liquid CDx is used to identify presence of genomic alterations for participant cohort assignment.
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.
  • Drug: Atezolizumab
    Atezolizumab IV infusion will be administered as per schedule specified in the respective arm.
    Other names:
    • Tecentriq
  • Drug: Tiragolumab
    Tiragolumab IV infusion will be administered as per schedule specified in the respective arm.
  • Diagnostic Test: FoundationOne®Liquid CDx
    FoundationOne®Liquid CDx is used to identify presence of genomic alterations for participant cohort assignment.
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.
  • Drug: Atezolizumab
    Atezolizumab IV infusion will be administered as per schedule specified in the respective arm.
    Other names:
    • Tecentriq
  • Drug: SY-5609
    SY-5609 will be administered by mouth as per schedule specified in the respective arm.
  • Diagnostic Test: FoundationOne®Liquid CDx
    FoundationOne®Liquid CDx is used to identify presence of genomic alterations for participant cohort assignment.
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.
  • Drug: Cetuximab
    Cetuximab IV will be administered as per schedule specified in the respective arm.
  • Drug: Divarasib
    Divarasib will be administered orally as per schedule specified in the respective arms.
    Other names:
    • GDC-6036
  • Drug: FOLFOX
    FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) IV will be administered as per schedule specified in the respective arm.
  • Diagnostic Test: FoundationOne®Liquid CDx
    FoundationOne®Liquid CDx is used to identify presence of genomic alterations for participant cohort assignment.
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.
  • Drug: Cetuximab
    Cetuximab IV will be administered as per schedule specified in the respective arm.
  • Drug: Divarasib
    Divarasib will be administered orally as per schedule specified in the respective arms.
    Other names:
    • GDC-6036
  • Diagnostic Test: FoundationOne®Liquid CDx
    FoundationOne®Liquid CDx is used to identify presence of genomic alterations for participant cohort assignment.
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.
  • Drug: Cetuximab
    Cetuximab IV will be administered as per schedule specified in the respective arm.
  • Drug: Divarasib
    Divarasib will be administered orally as per schedule specified in the respective arms.
    Other names:
    • GDC-6036
  • Drug: FOLFIRI
    FOLFIRI (leucovorin, 5-fluorouracil, irinotecan) IV will be administered as per schedule specified in the respective arm.
  • Diagnostic Test: FoundationOne®Liquid CDx
    FoundationOne®Liquid CDx is used to identify presence of genomic alterations for participant cohort assignment.
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.
  • Drug: Bevacizumab
    Bevacizumab IV will be administered as per schedule specified in the respective arm.
    Other names:
    • Avastin
  • Drug: Divarasib
    Divarasib will be administered orally as per schedule specified in the respective arms.
    Other names:
    • GDC-6036
  • Drug: FOLFOX
    FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) IV will be administered as per schedule specified in the respective arm.
  • Diagnostic Test: FoundationOne®Liquid CDx
    FoundationOne®Liquid CDx is used to identify presence of genomic alterations for participant cohort assignment.
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.
  • Drug: Bevacizumab
    Bevacizumab IV will be administered as per schedule specified in the respective arm.
    Other names:
    • Avastin
  • Drug: Divarasib
    Divarasib will be administered orally as per schedule specified in the respective arms.
    Other names:
    • GDC-6036
  • Drug: FOLFIRI
    FOLFIRI (leucovorin, 5-fluorouracil, irinotecan) IV will be administered as per schedule specified in the respective arm.
  • Diagnostic Test: FoundationOne®Liquid CDx
    FoundationOne®Liquid CDx is used to identify presence of genomic alterations for participant cohort assignment.

Recruiting Locations

Mayo Clinic Arizona
Phoenix, Arizona 85259

City of Hope Comprehensive Cancer Center
Duarte, California 91010

Cedars-Sinai Medical Center
Los Angeles, California 90048

UCLA
Los Angeles, California 90095

University of Colorado Cancer Center
Aurora, Colorado 80045

Rocky Mountain Cancer Centers, LLP
Lone Tree, Colorado 80124

Yale Cancer Center
New Haven, Connecticut 06520

Mayo Clinic in Florida
Jacksonville, Florida 32224

Moffitt Cancer Center
Tampa, Florida 33612

Illinois Cancer Specialists
Arlington Heights, Illinois 60005

Mary Bird Perkins Cancer Ctr
Baton Rouge, Louisiana 70809

Mayo Clinic Rochester
Rochester, Minnesota 55902

New York Cancer & Blood Specialists - New Hyde Park
New Hyde Park, New York 11042-1116

New York Cancer and Blood Specialists-Central Park Hematology & Oncology
New York, New York 10028

New York Cancer & Blood Specialists
Port Jefferson Station, New York 11776

New York Cancer & Blood Specialists - Bronx
The Bronx, New York 10469-5930

Hematology Oncology Salem
Salem, Oregon 97301

SCRI Oncology Partners
Nashville, Tennessee 37203

Texas Oncology - Northeast Texas
Denton, Texas 76201

Texas Oncology - Gulf Coast
Webster, Texas 77598-4420

More Details

Status
Recruiting
Sponsor
Hoffmann-La Roche

Study Contact

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

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.