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 Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Signed next-generation sequencing (NGS) Biomarker Eligibility Informed Consent Form - Age >= 18 years at time of signing Informed Consent Form - Biomarker eligibility as determined at a College of American Pathologists/clinical laboratory improvement amendments (CAP/CLIA)-certified or equivalently accredited diagnostic laboratory using a validated test - 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) - Availability of an archival tissue sample for exploratory biomarker research - Adequate hematologic and organ function within 14 days prior to initiation of study treatment - For women of childbearing potential: Must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment and agreement to remain abstinent 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 - 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 - Known HIV infection - 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 patient 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 patient compliance, or puts the patient at higher risk for treatment-related complications

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-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.
  • Drug: Inavolisib
    Inavolisib will be administered orally as per schedule specified in the respective arms.
  • Drug: Cetuximab
    Cetuximab IV will be administered as per specified in the respective arm.
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).
  • Drug: Inavolisib
    Inavolisib will be administered orally as per schedule specified in the respective arms.
  • Drug: Bevacizumab
    Bevacizumab IV will be administered as per specified in the respective arm.
    Other names:
    • Avastin
Experimental
Atezolizumab + Tiragolumab + Bevacizumab
Participants 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)
  • Drug: Bevacizumab
    Bevacizumab IV will be administered as per specified in the respective arm.
    Other names:
    • Avastin
  • Drug: Atezolizumab
    Atezolizumab IV infusion will be administered as per specified in the respective arm.
    Other names:
    • Tecentriq
  • Drug: Tiragolumab
    Tiragolumab IV infusion will be administered as per specified in the respective arm.
Experimental
Atezolizumab + Tiragolumab
Participants 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)
  • Drug: Atezolizumab
    Atezolizumab IV infusion will be administered as per specified in the respective arm.
    Other names:
    • Tecentriq
  • Drug: Tiragolumab
    Tiragolumab IV infusion will be administered as per specified in the respective arm.
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, or 5 mg by mouth for 7 days, followed by 7 days off. (Cycle length=28 days)
  • Drug: Atezolizumab
    Atezolizumab IV infusion will be administered as per specified in the respective arm.
    Other names:
    • Tecentriq
  • Drug: SY-5609
    SY-5609 will be administered by mouth as per specified in the respective arm.

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114

More Details

Status
Recruiting
Sponsor
Hoffmann-La Roche

Study Contact

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