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.
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
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
Primary outcome measure(s)
Objective Response Rate — Approximately 84 months Defined as the proportion of participants with a complete response or partial response, as determined by the investigator according to RECIST v1.1
Trial sites (84)
Facility
City
Region
Status
UAB Comprehensive Cancer Center
Birmingham
Alabama
Withdrawn
Mayo Clinic Arizona
Phoenix
Arizona
Recruiting
City of Hope Comprehensive Cancer Center
Duarte
California
Recruiting
cCare
Encinitas
California
Withdrawn
USC Norris Cancer Center
Los Angeles
California
Completed
Cedars-Sinai Medical Center
Los Angeles
California
Recruiting
UCLA
Los Angeles
California
Recruiting
Hoag Memorial Hospital Presbyterian
Newport Beach
California
Withdrawn
Stanford Cancer Center
Stanford
California
Completed
University of Colorado Cancer Center
Aurora
Colorado
Recruiting
Rocky Mountain Cancer Centers, LLP
Lone Tree
Colorado
Recruiting
Yale Cancer Center
New Haven
Connecticut
Recruiting
Eastern Ct Hema/Onco Assoc
Norwich
Connecticut
Withdrawn
Mayo Clinic in Florida
Jacksonville
Florida
Recruiting
Moffitt Cancer Center
Tampa
Florida
Recruiting
Illinois Cancer Specialists
Arlington Heights
Illinois
Recruiting
Mary Bird Perkins Cancer Ctr
Baton Rouge
Louisiana
Recruiting
Massachusetts General Hospital
Boston
Massachusetts
Completed
Karmanos Cancer Institute
Detroit
Michigan
Withdrawn
Mayo Clinic Rochester
Rochester
Minnesota
Recruiting
New York Cancer & Blood Specialists - New Hyde Park
New Hyde Park
New York
Recruiting
New York Cancer and Blood Specialists-Central Park Hematology & Oncology
New York
New York
Recruiting
New York Cancer & Blood Specialists
Port Jefferson Station
New York
Recruiting
New York Cancer & Blood Specialists - Bronx
The Bronx
New York
Recruiting
Duke University Medical Center
Durham
North Carolina
Completed
Hematology Oncology Salem
Salem
Oregon
Recruiting
UPMC - Hillman Cancer Center
Pittsburgh
Pennsylvania
Active Not Recruiting
Sarah Cannon Research Institute / Tennessee Oncology
Nashville
Tennessee
Completed
SCRI Oncology Partners
Nashville
Tennessee
Recruiting
Vanderbilt University Medical Center
Nashville
Tennessee
Completed
Texas Oncology - Northeast Texas
Denton
Texas
Recruiting
Lumi Research
Kingwood
Texas
Withdrawn
Texas Oncology - Gulf Coast
Webster
Texas
Recruiting
Swedish Cancer Inst.
Seattle
Washington
Completed
Medical Oncology Associates
Spokane
Washington
Withdrawn
Peter Maccallum Cancer Centre
Melbourne
Victoria
Recruiting
Princess Margaret Cancer Center
Toronto
Ontario
Active Not Recruiting
Jewish General Hospital
Montreal
Quebec
Withdrawn
McGill University Health Center
Montreal
Quebec
Withdrawn
Herlev Hospital, Afdeling for Kræftbehandling, Center for Kræftforskning, Klinisk Forskningsenhed
Herlev
Denmark
Recruiting
+ 44 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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