Atezolizumab + Bevacizumab + Tiragolumab for Colorectal Cancer

Overseen By Puja Gupta Poddar

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Must be taking: Fluoropyrimidine, Oxaliplatin, Irinotecan, EGFR inhibitors

Must not be taking: Antidepressants, Immunosuppressants, Anticoagulants, others

Disqualifiers: Autoimmune disease, CNS metastases, Cardiovascular dysfunction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 24

Duration: Up to 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of three drugs to determine their effectiveness in treating advanced colorectal cancer that cannot be surgically removed. Researchers aim to assess the treatment's effectiveness, safety, and interaction with the immune system. Suitable candidates for this trial have advanced colorectal cancer that has not responded to previous treatments. Some participants will undergo tumor biopsies (a small sample of tissue taken for study), while others will not, to better understand the treatment effects. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial information does not clearly state if you need to stop your current medications. However, it mentions that certain medications, like systemic immunosuppressive drugs, may need to be stopped before starting the study treatment. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of atezolizumab, bevacizumab, and tiragolumab has been tested before. One study examined how well patients tolerated these drugs together. Although the study did not find significant improvements in certain cancer outcomes, it provided important safety information.

Regarding safety, earlier studies have generally found this drug combination to be well-tolerated. Some patients experienced side effects, but these were mostly manageable. Common issues included fatigue and changes in lab test results, while serious problems were less common.

This trial is in an intermediate phase, indicating some evidence of safety for humans, but more information is needed to confirm its safety for wider use. Researchers will closely monitor participants to address any side effects promptly. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Atezolizumab, Bevacizumab, and Tiragolumab for colorectal cancer because it offers a novel approach that isn't typical of current treatments. Most standard treatments, like chemotherapy and targeted therapies, focus on directly killing cancer cells or blocking blood supply. However, this combination therapy includes Atezolizumab and Tiragolumab, which are immune checkpoint inhibitors that help the immune system better recognize and attack cancer cells. Bevacizumab adds to this by inhibiting blood vessel growth that tumors need to thrive. This multi-pronged strategy could enhance effectiveness and potentially improve patient outcomes by leveraging the body's own defense mechanisms against cancer.

What evidence suggests that this trial's treatments could be effective for colorectal cancer?

Research has shown that adding tiragolumab to atezolizumab and bevacizumab may help treat advanced cancers. One study found that this combination improved treatment efficacy. Although it didn't enhance outcomes for some liver cancers, it might work differently for colorectal cancer patients. In this trial, participants will receive atezolizumab, bevacizumab, and tiragolumab. Atezolizumab and bevacizumab have been tested together in various cancers and have shown some benefits. Tiragolumab helps the immune system fight cancer cells. This combination aims to attack cancer in different ways, potentially offering a new treatment option. ^{1 3 4 6 7}

Who Is on the Research Team?

Hannah Robinson, MD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

This trial is for individuals with advanced colorectal cancer that has not responded to changes in their DNA repair system (microsatellite stable). Participants will receive a combination of three drugs and must be willing to undergo regular checkups, lab tests, imaging, and possibly tumor biopsies.

Inclusion Criteria

Able to sign the consent form

Negative hepatitis B surface antigen (HBsAg) test at screening

Negative hepatitis C virus (HCV) antibody test at screening or specific criteria for positive HCV antibody test

Exclusion Criteria

I can understand and follow the study's requirements.

My cancer has been tested for MSI-H or dMMR, or the status is unknown.

I have brain metastases that are either untreated, worsening, or stable if previously treated.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a fixed-dose regimen of atezolizumab, bevacizumab, and tiragolumab every 21 days. Treatment continues until disease progression, unacceptable toxicity, or other specified criteria.

Up to 24 months

Every 21 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Correlative Studies

Participants in Cohort A undergo pre-treatment and on-treatment tumor biopsies for correlative analyses.

Approximately 42 days

Biopsies at pre-treatment and cycle 3, day 1

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Bevacizumab
• Tiragolumab

Trial Overview The study is testing the effectiveness and safety of combining atezolizumab, bevacizumab, and tiragolumab as a treatment for advanced colorectal cancer. It also examines how this combination affects the immune system of patients.

How Is the Trial Designed?

Group I: Treatment without Biopsy Experimental Treatment 3 Interventions

In Cohort B, no study-related biopsies will be obtained. Outside of pre- and on-treatment biopsies, patients in Cohort A and Cohort B will receive identical treatments and assessments.

Group II: Treatment with Biopsy Experimental Treatment 5 Interventions

Patients in Cohort A will undergo pre-treatment and on-treatment tumor biopsies for correlative analyses, with on-treatment biopsies obtained at cycle 3, day 1 (C3D1) +/- 3 days of treatment.

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06784947

Study Details | NCT06784947 | Trial of Atezolizumab ... The goal of this study is to learn if a new combination treatment is effective for patients with microsatellite stable, advanced colorectal cancer.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2949819825000950

Preoperative immunotherapy with atezolizumab and ... Hepatic resection offers long-term survival in some patients with CRC liver metastases (CRLM), but recurrence rates remain high (50%-75% within 2 years).

3. digestivecancers.eu digestivecancers.eu/progress-in-liver-and-bile-duct-cancer-new-insights-from-esmo-2025/

Progress in Liver and Bile Duct Cancer: New Insights from ... Key takeaway: Adding tiragolumab to atezolizumab and bevacizumab did not improve outcomes in advanced liver cancer. The current two-drug ...

4. thelancet.com thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(24)00679-X.pdf

Tiragolumab in combination with atezolizumab and Results from our study suggest improved clinical activity when tiragolumab is added to atezolizumab plus bevacizumab for patients with ...

5. onclive.com onclive.com/view/dr-finn-on-tiragolumab-plus-atezolizumab-and-bevacizumab-in-hcc

Dr Finn on Tiragolumab Plus Atezolizumab and ... - OncLive Tiragolumab is an anti-TIGIT antibody that emerged as a promising combination component based on prior data from MORPHEUS-Liver, Finn said.

6. onclive.com onclive.com/view/tiragolumab-atezolizumab-bevacizumab-fails-to-significantly-improve-pfs-in-advanced-metastatic-hcc

Tiragolumab/Atezolizumab/Bevacizumab Fails to ... Tiragolumab plus atezolizumab and bevacizumab did not significantly improve PFS in advanced HCC compared to placebo with atezolizumab and ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06784947?cond=%22Colorectal%20Adenocarcinoma%22&intr=%22endothelial%20growth%20factors%22&viewType=Table&rank=4

Trial of Atezolizumab, Bevacizumab, and Tiragolumab in ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...