Immunotherapies in Combination With Stereotactic Body Radiation Radiotherapy in Microsatellite Stable (MSS) Metastatic Colorectal Cancer (mCRC)

NCT06603818 | Withdrawn Phase 2 FDA Drug

• 2 other identifiers: 10001589001589-C
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Metastatic colorectal cancer (mCRC) is cancer that has spread beyond the colon and rectum. Most people with mCRC die within 5 years. New immune-based treatments are making progress with some types of colon cancer. But these treatments do little for people with a type of cancer that is microsatellite stable (MSS). MSS is a specific cancer biomarker. Better treatments are needed. Objective: To test 2 drugs (tiragolumab and atezolizumab) combined with radiation therapy in people with MSS mCRC. Eligibility: People aged 18 years and older with MSS mCRC. Design: Participants will be screened. They will have a physical exam with blood tests. They will have imaging scans and a test of their heart function. They will provide a tissue sample from their tumor; if one is not already available, a new sample will be taken. Their ability to perform normal tasks will be assessed. Tiragolumab and atezolizumab are both administered through a tube attached to a needle inserted into a vein. Participants will receive both drugs on day 1 of 3-week treatment cycles. Each study visit should last about 8 hours. Participants will receive radiation therapy on days 1, 3, and 5 of cycle 1 only. Blood samples and rectal swabs will be collected on day 1 of every cycle. Imaging scans will be repeated every 9 weeks. Additional tumor samples may be taken during treatment. Treatment will continue for up to 2 years. Participants will have a follow-up visit 1 month after treatment ends. Follow-up visits will continue every 3 months for 1 more year.

Conditions

Microsatellite Stable Metastatic Colorectal Cancer; Metastatic Colorectal Cancer; Colorectal Cancer

Keywords

Stereotactic Body Radiation Radiotherapy; Immunotherapy; Radiation Therapy

Outcome Measures

Primary Outcomes (2)

• Confirm the recommended phase II dose (RP2D) of the combination therapy

  Dose-limiting toxicities (DLTs) will be collected and reported by type, grade and frequency.

  Start of therapy through cycle 1 day 21

• Determine the proportion of participants without progression after 9 weeks of the combination therapy

  Proportion of participants attaining 9-week progression-free survival will be evaluated and reported along with a 95% confidence interval.

  After 9 weeks of treatment

Secondary Outcomes (5)

• Safety

  Start of therapy through 28 days after last study treatment intervention.

• Tolerability

  Start of therapy through 28 days after last study treatment intervention.

• Best overall response (Partial Response + Complete Response) according to RECIST v1.1

  Every 9 weeks during the study treatment and every 3 months after that until progression or 3 years after treatment initiation

• Progression Free Survival

  Every 9 weeks during the study treatment and every 3 months after that until progression or 3 years after treatment initiation

• Overall Survival

  Start of therapy until death or 3 years after treatment initiation

Study Arms (1)

Arm 1

EXPERIMENTAL

Atezolizumab and tiragolumab IV every 3 weeks cycle plus SBRT on Days 1, 3, and 5 of Cycle 1

Biological: Tiragolumab; Biological: Atezolizumab; Radiation: Stereotactic Body Radiation Therapy (SBRT)

Interventions

Tiragolumab BIOLOGICAL

Tiragolumab is given intravenously (IV) every 3 weeks (21-day cycles) for up to 2 years

Arm 1

Atezolizumab BIOLOGICAL

Atezolizumab is given intravenously (IV) every 3 weeks (21-day cycles) for up to 2 years

Arm 1

Stereotactic Body Radiation Therapy (SBRT) RADIATION

SBRT will occur on Days 1, 3, and 5 of Cycle 1 only

Arm 1

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed colorectal cancer (CRC) by the NCI Laboratory of Pathology (LP). Note: Participants must provide tumor sample or be willing to undergo biopsy to confirm the diagnosis.
• Evidence of metastatic involvement.
• History of microsatellite stable (MSS) status.
• Age \>= 18 years.
• Weight \> 35 kg.
• ECOG performance status \<= 1
• Must have measurable disease, per RECIST 1.1
• At least 2 lesions present, one of which must be amenable to SBRT and second lesion outside the radiation field must serve as target lesion to evaluate measurable disease.
• Must have progression of disease, been treated or intolerant to at least 2 lines of systemic standard of care treatment in the metastatic setting (e.g., fluoropyrimidine-, oxaliplatin-, or irinotecan-based therapy \[unless ineligible for any of these drugs\]).
• Participants with a history of RAS wild-type tumor must have progressed, been intolerant of OR refused anti-EGFR based treatment.
• Participants must have adequate organ and marrow function as defined below:
• Leukocytes \>= 3,000/microL
• Absolute neutrophil count \>= 1,500/microL
• Lymphocyte count \> 500/microL
• Platelets \>= 100,000/microL without transfusion or at least \> 48 hours post-completion of blood transfusion

You may not qualify if:

• Disease amenable to curative resection.
• Chemotherapy, radiation therapy, or biologic therapy within 3 weeks (or \>= 5 half-lives, whichever is shorter) prior to starting the study therapy.
• Treatment with an investigational therapy within 42 days prior to starting the study therapy.
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and IL-2) within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to starting the study therapy.
• History of prior treatment with TIGIT-directed treatment agents or other types of immunotherapies (e.g., prior treatment with CD137 agonists or investigational immune checkpoint blockade therapies, including anti-TIGIT, anti-PD1/anti-PDL1, anti-CTLA-4, anti-LAG3).
• Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor-alpha \[TNF-alpha\] agents) within 2 weeks prior to starting the study therapy, or anticipation of a need for systemic immunosuppressive medication during study therapy, with the following exceptions:
• acute, low-dose systemic immunosuppressant medication (\< 10 mg of prednisone daily) or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy).
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to starting the study therapy.
• Treatment with a live, attenuated vaccine within 4 weeks prior to starting the study therapy.
• Major surgery within 4 weeks prior to starting the study therapy.
• Prior allogeneic stem cell or solid organ transplantation.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to tiragolumab and atezolizumab or other agents used in a study or known hypersensitivity to Chinese hamster ovary cell products.
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
• History of central nervous system (CNS) metastasis or leptomeningeal disease.
• Current uncontrolled tumor-related pain. Participants requiring pain medication must be on a stable regimen at study entry.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Tiragolumab; atezolizumab; Radiosurgery

Condition Hierarchy (Ancestors)

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)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Tim F Greten, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2024
• First Posted: September 19, 2024
• Study Start: August 15, 2025
• Primary Completion: August 15, 2025
• Study Completion: August 15, 2025
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data from this study may be requested after the completion of the primary endpoint
• Access Criteria: Data from this study may be requested by contacting the NCI Principal Investigator@@@@@@

Locations

US (1)