What side effects are associated with this type of intervention?

Common treatments for colorectal cancer, particularly targeted therapies and immunotherapy, have distinct side effect profiles. Targeted therapies, such as bevacizumab, cetuximab, and panitumumab, can cause hypertension, proteinuria, skin rash, and infusion-related reactions. Immunotherapy, including PD-1 inhibitors like pembrolizumab and nivolumab, may lead to immune-related adverse events such as colitis, hepatitis, pneumonitis, and endocrinopathies. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several targeted therapies and immunotherapies for the treatment of colorectal cancer. Notable targeted therapies include cetuximab and panitumumab, which target the epidermal growth factor receptor (EGFR), and bevacizumab, which targets vascular endothelial growth factor (VEGF). Immunotherapy options include pembrolizumab and nivolumab, which are immune checkpoint inhibitors targeting PD-1, used particularly in patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) tumors. These treatments align with the approaches being studied in the INTRINSIC trial, which evaluates the safety and efficacy of targeted therapies and immunotherapy in biomarker-positive metastatic colorectal cancer patients.

What other types of research exist?

Promising novel alternatives to targeted therapies or immunotherapy for colorectal cancer patients in 2024 include: 1) Combination therapies involving novel agents such as antibody-drug conjugates (ADCs) and bispecific antibodies, which target multiple pathways simultaneously. 2) Advanced chemotherapy regimens that incorporate new cytotoxic agents with improved efficacy and safety profiles. 3) Personalized medicine approaches using next-generation sequencing (NGS) to identify unique genetic mutations and tailor treatments accordingly. 4) Emerging modalities like oncolytic virus therapy, which uses genetically modified viruses to selectively infect and kill cancer cells while stimulating an anti-tumor immune response.

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Monoclonal Antibodies

Targeted Therapies + Immunotherapy for Colorectal Cancer

Q: What is the mechanism of action of this treatment?

The most common treatments for colorectal cancer include targeted therapies and immunotherapy. Targeted therapies interfere with specific molecules involved in tumor growth and progression, such as blocking the epidermal growth factor receptor (EGFR) or inhibiting angiogenesis with agents like bevacizumab. Immunotherapy boosts the body's natural defenses to fight cancer by using immune checkpoint inhibitors that target proteins like PD-1/PD-L1 or CTLA-4, helping the immune system recognize and attack cancer cells. These mechanisms are crucial for colorectal cancer patients as they allow for personalized treatment plans, potentially leading to more effective and less toxic therapies.

Phase 1

Waitlist Available

Research Sponsored by Hoffmann-La Roche

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histologically confirmed adenocarcinoma originating from the colon or rectum

Metastatic disease

Must not have

Clinically significant and active liver disease

Any systemic anti-cancer treatment within 2 weeks or 5 half-lives (whichever is shorter) prior to start of study treatment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up approximately 60 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing the safety and effectiveness of drugs that either target cancer cells directly or help the immune system fight cancer. It focuses on patients with advanced colorectal cancer whose tumors have certain biomarkers. The goal is to see if these treatments work better for these specific patients.

Who is the study for?

Adults with metastatic colorectal cancer who are in relatively good health (ECOG <=1) and have a life expectancy of at least 3 months. They must have biomarker-positive tumors as per specific arm definitions, measurable disease, and adequate organ function. Participants need to agree to use contraception and not be pregnant or breastfeeding. Those with severe medical conditions, active infections, uncontrolled pain or complications from prior treatments are excluded.

What is being tested?

The trial is testing the safety and effectiveness of various targeted therapies and immunotherapies—either alone or in combination—for metastatic colorectal cancer patients with certain biomarkers. These include Bevacizumab, Tiragolumab, Atezolizumab, Cetuximab among others along with chemotherapy regimens like FOLFOX and FOLFIRI.

What are the potential side effects?

Potential side effects may include allergic reactions to medications; issues affecting blood cells leading to increased infection risk; fatigue; liver problems; digestive disturbances such as nausea or diarrhea; skin reactions from drugs like Cetuximab; high blood pressure due to Bevacizumab.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer is a type that started in the colon or rectum.

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My cancer has spread to other parts of my body.

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I am 18 years old or older.

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I have received treatments for cancer that has spread.

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I am fully active or can carry out light work.

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I agree to either not have sex or use birth control, and not donate sperm.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have an active liver condition that affects my health.

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I haven't had any cancer treatments in the last 2 weeks or 5 half-lives, whichever is shorter.

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I have had cancer spread to the lining of my brain or spinal cord.

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I frequently need procedures to remove excess fluid from my body.

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I have pain from my cancer that isn't relieved by treatment.

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I have brain metastases that are causing symptoms or getting worse.

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I am fully recovered from any past surgeries before starting the study treatment.

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I have high calcium levels in my blood that are causing symptoms.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ approximately 60 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~approximately 60 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and approximately 60 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Objective Response Rate

Secondary study objectives

Disease Control Rate

Duration of Response

Percentage of Participants with Adverse Events (AEs)

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

8Treatment groups

Experimental Treatment

Group I: Inavolisib + CetuximabExperimental Treatment2 Interventions

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.

Group II: Inavolisib + BevacizumabExperimental Treatment2 Interventions

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).

Group III: Divarasib + Cetuximab + FOLFOXExperimental Treatment3 Interventions

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)

Group IV: Divarasib + Cetuximab + FOLFIRIExperimental Treatment3 Interventions

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)

Group V: Divarasib + CetuximabExperimental Treatment2 Interventions

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)

Group VI: Atezolizumab + Tiragolumab + BevacizumabExperimental Treatment3 Interventions

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)

Group VII: Atezolizumab + TiragolumabExperimental Treatment2 Interventions

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)

Group VIII: Atezolizumab + SY-5609Experimental Treatment2 Interventions

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) Open in the United States only.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Atezolizumab

2016

Completed Phase 3

~5860

Bevacizumab

2013

Completed Phase 4

~5540

Tiragolumab

2019

Completed Phase 3

~1810

Cetuximab

2011

Completed Phase 3

~2480

SY-5609

2021

Completed Phase 1

~530

Inavolisib

2021

Completed Phase 2

~680

Divarasib

2021

Completed Phase 1

~430

FOLFOX

2009

Completed Phase 3

~4560

FOLFIRI

2005

Completed Phase 3

~5860

0 / 14Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for colorectal cancer include targeted therapies and immunotherapy. Targeted therapies interfere with specific molecules involved in tumor growth and progression, such as blocking the epidermal growth factor receptor (EGFR) or inhibiting angiogenesis with agents like bevacizumab. Immunotherapy boosts the body's natural defenses to fight cancer by using immune checkpoint inhibitors that target proteins like PD-1/PD-L1 or CTLA-4, helping the immune system recognize and attack cancer cells. These mechanisms are crucial for colorectal cancer patients as they allow for personalized treatment plans, potentially leading to more effective and less toxic therapies.