Trial of Atezolizumab, Bevacizumab, and Tiragolumab in Patients With Microsatellite Stable, Metastatic Colorectal Cancer

NCT06784947 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 24-0547.cc
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to learn if a new combination treatment is effective for patients with microsatellite stable, advanced colorectal cancer. The study treatment combines 3 drugs: atezolizumab, bevacizumab, and tiragolumab. The main questions the study aims to answer are:

1. 1.Does the study treatment effectively treat colorectal cancer?
2. 2.Is the study treatment safe for patients with colorectal cancer?
3. 3.How does the study treatment effect the immune system in patients with colorectal cancer?

Conditions

Microsatellite Stable (MSS) Colorectal Cancer (CRC); Metastatic Colorectal Cancer (CRC); Colorectal Cancer Stage IV

Keywords

immunotherapy; microsatellite stable colorectal cancer; tiragolumab; metastatic colorectal cancer; atezolizumab; bevacizumab

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  The primary outcome of this trial is objective response rate (ORR), defined as the proportion of patients who achieve a complete or partial response to treatment according to RECIST v1.1 criteria.

  From time of study start to time of best response, up to 24 months

Secondary Outcomes (6)

• Progression Free Survival (PFS)

  From time of study start until disease progression or death, whichever comes first; up to 24 months

• Overall Survival (OS)

  From time of study start until death by any cause, up to 24 months

• Safety measured by adverse events

  From time of study start until time of study end, up to 24 months

• Impact of Liver Metastases on Treatment Response- ORR

  From time of study start to time of best response (ORR), up to 24 months

• Impact of Liver Metastases on Treatment Response- PFS

  From time of study start until disease progression or death, whichever comes first; up to 24 months

Other Outcomes (3)

• Disease Control Rate (DCR)

  From time of study start to time of best response, up to 24 months

• Duration of Response (DOR)

  From time of response to treatment through time of progression or death, up to 24 months

• Immune Correlates of Response

  Testing will be performed using samples collected prior to the first study treatment and at the time of the third study treatment, approximately 42 days later.

Study Arms (2)

Treatment with Biopsy

EXPERIMENTAL

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.

Procedure: Pre-Treatment Biopsy; Procedure: On-Treatment Biopsy; Drug: Tiragolumab; Drug: Atezolizumab; Drug: Bevacizumab

Treatment without Biopsy

EXPERIMENTAL

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.

Drug: Tiragolumab; Drug: Atezolizumab; Drug: Bevacizumab

Interventions

Pre-Treatment Biopsy PROCEDURE

The pre-treatment biopsy should be performed at least 3 days prior to C1D1 of treatment.

Treatment with Biopsy

On-Treatment Biopsy PROCEDURE

While the acceptable window for the C3D1 biopsy is ±3 days, it is preferred that the biopsy occurs following all treatments on C3D1.

Treatment with Biopsy

Tiragolumab DRUG

Tiragolumab is a human monoclonal antibody targeting the co-inhibitory molecule and immune checkpoint inhibitor T-cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif (ITIM) domains (TIGIT), with potential immune checkpoint inhibitory activity. This treatment may help the immune system attack cancer cells.

Treatment with Biopsy; Treatment without Biopsy

Atezolizumab DRUG

Atezolizumab is a type of targeted therapy drug called an immune checkpoint inhibitor. It is a monoclonal antibody that works by binding to the protein PD-L1 (programmed death) on the surface of some cancer cells, which keeps cancer cells from suppressing the immune system. This allows the immune system to attack and kill the cancer cells.

Treatment with Biopsy; Treatment without Biopsy

Bevacizumab DRUG

Bevacizumab works by blocking a protein called Vascular Endothelial Growth Factor (VEGF), which some cancer cells produce in large amounts. Blocking VEGF may prevent the growth of new blood vessels that tumors need to grow, and may help improve the immune response in the tumor. Bevacizumab is a type of targeted therapy called an angiogenesis inhibitor.

Treatment with Biopsy; Treatment without Biopsy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to sign the consent form.
• Stated willingness and ability to comply with all study procedures and be available for the duration of the study.
• ≥ 18 years at the time of informed consent.
• Biopsy confirmed, unresectable, metastatic colorectal adenocarcinoma.
• Measurable disease (disease that can be viewed and measured on scans), as assessed by the investigator per RECIST v1.1.
• If in Cohort A, (1) the patient must state willingness to undergo pre- and on-treatment biopsies, and (2) the patient's disease must be amenable to biopsy.
• Eastern Cooperative Oncology Group performance status of 0-2.
• Documented microsatellite stable and/or proficient mismatch repair status.
• Documented testing for KRAS, NRAS, and BRAF mutation status.
• Progression on or intolerance to prior therapy for unresectable, metastatic CRC including at least (1) fluoropyrimidine, oxaliplatin, and irinotecan chemotherapy AND (2) EGFR inhibitor therapy for patients with KRAS/NRAS/BRAF wild-type, left-sided disease.
• Adequate hematologic and end organ function, defined by laboratory results obtained within 28 days prior to the first dose of study treatment.
• ANC ≥ 1.2 × 10\^9/L
• Lymphocyte count ≥ 0.5 x 10\^9/L
• Platelet count ≥ 100 × 10\^9/L, without transfusion in the prior week.
• Hemoglobin ≥ 9 g/dL; patients may be transfused to meet this criterion.

You may not qualify if:

• Illness or condition that may interfere with a patient's capacity to understand, follow, and/or comply with study procedures.
• Known microsatellite instability-high or deficient mismatch repair status, or unknown status for both MSI and MMR.
• Prior testing documenting a BRAF V600E mutation, or unknown testing results for KRAS, NRAS, and BRAF.
• A limited number of patients with active liver metastases will be permitted in this trial. Those with a history of definitively treated liver metastases with treatment occurring at least 6 months prior to enrollment with no evidence of metastatic disease in the liver on subsequent imaging may be eligible to enroll as a patient without active liver disease.
• Known symptomatic, untreated, or actively progressing central nervous system metastases. Asymptomatic patients with treated CNS lesions are eligible, provided that additional criteria are met.
• History of leptomeningeal disease or carcinomatous meningitis.
• Spinal cord compression not definitively treated with surgery and/or radiation.
• Uncontrolled tumor-related pain. Patients requiring pain medication must be on a stable regimen at study entry.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
• History of malignancy other than colorectal cancer within 3 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death, such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, or ductal carcinoma in situ.
• Active autoimmune disease, history of autoimmune disease requiring treatment with corticosteroids, disease modifying agents, and/or immunosuppressive therapy, or immune deficiency including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the exceptions listed below:
• Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study.
• Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only are eligible for the study provided all of following conditions are met:
• Rash must cover \< 10% of body surface area.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Universtiy of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Spinocerebellar Degenerations; Colorectal Neoplasms

Interventions

Tiragolumab; atezolizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Hannah Robinson, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2025
• First Posted: January 20, 2025
• Study Start: March 25, 2025
• Primary Completion: September 18, 2025
• Study Completion (Estimated): May 1, 2028
• Last Updated: October 2, 2025

Record last verified: 2025-10

Locations

US (1)