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

Roche

Status and phase: Enrolling; Phase 1

Conditions: Metastatic Colorectal Cancer

Treatments: Drug: Inavolisib; Drug: Bevacizumab; Drug: FOLFIRI; Drug: SY-5609; Drug: Tiragolumab; Drug: Atezolizumab; Drug: FOLFOX; Drug: Cetuximab; Drug: Divarasib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04929223

2023-505163-37-00 (Other Identifier)

WO42758

2021-001207-33 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 542 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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542 participants in 10 patient groups

Inavolisib + Cetuximab

Experimental group

Description:

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 active, and not recruiting participants.

Treatment:

Drug: Cetuximab

Drug: Inavolisib

Inavolisib + Bevacizumab

Experimental group

Description:

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 active, and not recruiting participants.

Treatment:

Drug: Bevacizumab

Drug: Inavolisib

Atezolizumab + Tiragolumab + Bevacizumab

Experimental group

Description:

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.

Treatment:

Drug: Tiragolumab

Drug: Atezolizumab

Drug: Bevacizumab

Atezolizumab + Tiragolumab

Experimental group

Description:

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.

Treatment:

Drug: Tiragolumab

Drug: Atezolizumab

Atezolizumab + SY-5609

Experimental group

Description:

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.

Treatment:

Drug: Atezolizumab

Drug: SY-5609

Divarasib + Cetuximab + FOLFOX

Experimental group

Description:

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.

Treatment:

Drug: Divarasib

Drug: Cetuximab

Drug: FOLFOX

Divarasib + Cetuximab

Experimental group

Description:

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.

Treatment:

Drug: Divarasib

Drug: Cetuximab

Divarasib + Cetuximab + FOLFIRI

Experimental group

Description:

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.

Treatment:

Drug: Divarasib

Drug: Cetuximab

Drug: FOLFIRI

Divarasib + Bevacizumab + FOLFOX

Experimental group

Description:

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.

Treatment:

Drug: Divarasib

Drug: FOLFOX

Drug: Bevacizumab

Divarasib + Bevacizumab + FOLFIRI

Experimental group

Description:

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.

Treatment:

Drug: Divarasib

Drug: FOLFIRI

Drug: Bevacizumab