A Study Evaluating the Safety and Efficacy of Targeted Therapies in Subpopulations of Patients With Metastatic Colorectal Cancer (INTRINSIC)
Phase 1
Recruiting
- Conditions
- Metastatic Colorectal Cancer
- Interventions
- Registration Number
- NCT04929223
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 542
Inclusion Criteria
Not provided
Exclusion Criteria
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Inavolisib + Cetuximab 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 active, and not recruiting participants. Inavolisib + Bevacizumab 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 active, and not recruiting participants. Atezolizumab + Tiragolumab + Bevacizumab 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. Atezolizumab + Tiragolumab + Bevacizumab Atezolizumab 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. Atezolizumab + Tiragolumab + Bevacizumab Tiragolumab 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. Atezolizumab + Tiragolumab Atezolizumab 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. Atezolizumab + Tiragolumab 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. Atezolizumab + SY-5609 Atezolizumab 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. Atezolizumab + SY-5609 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. Divarasib + Cetuximab + FOLFOX Cetuximab 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. Divarasib + Cetuximab + FOLFOX 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. Divarasib + Cetuximab 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. Divarasib + Cetuximab + FOLFIRI Cetuximab 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. Divarasib + Cetuximab + FOLFIRI 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. Divarasib + Bevacizumab + FOLFOX Bevacizumab 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. Divarasib + Bevacizumab + FOLFOX 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. Divarasib + Bevacizumab + FOLFIRI Bevacizumab 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. Divarasib + Bevacizumab + FOLFIRI 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. Divarasib + Cetuximab + FOLFOX Divarasib 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. Divarasib + Cetuximab Divarasib 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. Divarasib + Cetuximab + FOLFIRI Divarasib 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. Divarasib + Bevacizumab + FOLFOX Divarasib 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. Divarasib + Bevacizumab + FOLFIRI Divarasib 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. Inavolisib + Cetuximab Inavolisib 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. Inavolisib + Bevacizumab Inavolisib 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.
- Primary Outcome Measures
Name Time Method 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
- Secondary Outcome Measures
Name Time Method Duration of Response Approximately 84 months Defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1
Disease Control Rate Approximately 84 months Defined as the proportion of participants with stable disease, or a complete or partial response, as determined by the investigator according to RECIST v1.1
Percentage of Participants with Adverse Events (AEs) Approximately 84 months Percentage of participants with adverse events.
Plasma Concentrations of Divarasib At pre-defined intervals from first administration of study drug up to approximately 84 months Plasma concentration of divarasib for divarasib + cetuximab + FOLFOX, divarasib + cetuximab, and divarasib + cetuximab+ FOLFIRI, Divarasib + Bevacizumab + FOLFOX, Divarasib + Bevacizumab + FOLFIRI treatment arms.
Recommended Dose of Divarasib in Combination with Bevacizumab and FOLFOX Approximately 84 months Recommended dose of divarasib in combination with bevacizumab and FOLFOX based on the totality of safety, efficacy and PK data.
Recommended Dose of Divarasib in Combination with Bevacizumab and FOLFIRI Approximately 84 months Recommended dose of divarasib in combination with bevacizumab and FOLFIRI based on the totality of safety, efficacy and PK data.
Trial Locations
- Locations (73)
UAB Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States
Mayo Clinic Arizona
🇺🇸Phoenix, Arizona, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
cCare
🇺🇸Encinitas, California, United States
USC Norris Cancer Center
🇺🇸Los Angeles, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
UCLA
🇺🇸Los Angeles, California, United States
Hoag Memorial Hospital Presbyterian
🇺🇸Newport Beach, California, United States
Stanford Cancer Center
🇺🇸Stanford, California, United States
University of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
Scroll for more (63 remaining)UAB Comprehensive Cancer Center🇺🇸Birmingham, Alabama, United States