Ignite Creation Date:
2025-12-25 @ 4:36 AM
Ignite Modification Date:
2025-12-26 @ 3:38 AM
Study NCT ID:
NCT06603818
Status:
RECRUITING
Last Update Posted:
2025-08-19
First Post:
2024-09-17
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Immunotherapies in Combination With Stereotactic Body Radiation Radiotherapy in Microsatellite Stable (MSS) Metastatic Colorectal Cancer (mCRC)
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase II Study of Immunotherapies (Tiragolumab and Atezolizumab) in Combination With Stereotactic Body Radiation Radiotherapy in Microsatellite Stable (MSS) Metastatic Colorectal Cancer (mCRC)
Status:
RECRUITING
Status Verified Date:
2025-07-16
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
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.
Detailed Description:
Background:
* Metastatic colorectal cancer (mCRC) is incurable for most patients and carries a poor diagnosis.
* Immune-based approaches in solid tumor malignancies have seen much progress but these have limited efficacy for microsatellite stable (MSS) mCRC.
* The Gastrointestinal Malignancies Section at NCI conducted a Pilot Study of the PD-1 Targeting Agent AMP-224 with low-dose cyclophosphamide and stereotactic body radiation therapy (SBRT) that supports potential antitumor efficacy of the combination of immunotherapy and radiation in MSS mCRC (NCT02298946).
* T cell immunoreceptor with Ig and ITIM domains (TIGIT) is an inhibitory receptor expressed in multiple cancers on tumor-infiltrating cytotoxic T cells, helper T cells, natural killer (NK) cells, and regulatory T cells. Its main ligand, CD155, is expressed on tumor-infiltrating myeloid cells and upregulated on cancer cells, contributing to local immune-surveillance suppression.
* Among inhibitory immune checkpoint molecules, a unique property of TIGIT blockade is that it enhances not only anti-tumor effector T-cell responses, but also NK-cell responses, and reduces the suppressive capacity of regulatory T cells.
* Pre-clinical studies show that the co-blockade of TIGIT and the programmed cell death protein 1 (PD-1) / programmed cell death ligand 1 (PD-L1) pathway may lead to decreased tumor volume. Notably, this has been observed in anti-PD-1 resistant tumor models.
* Preclinical and clinical evidence suggests further increased benefit to the double immune checkpoint blockade through increased expression of PD-L1 and neoantigens in response to SBRT.
* Early results from clinical trials suggest clinical activity of anti-TIGITplus anti-PD-L1 in solid tumors and the effect of combining immunotherapy with radiation in heavily pretreated MSS mCRC patients providing a proof of concept that radiation enhances immunotherapy response.
* A combination of anti-PD-L1, anti-TIGIT, and SBRT may increase CRC susceptibility to immune therapy given the promising activity of anti-TIGIT in combination with anti-PDL1 in preclinical studies of mice bearing subcutaneous CT26 colon tumors.
Primary Objectives:
* To confirm the Recommended Phase II dose (RP2D) of the combination therapy (tiragolumab and atezolizumab plus SBRT) in participants with MSS mCRC (Part A)
* To determine the proportion of participants without progression after 9 weeks of the combination therapy (tiragolumab and atezolizumab plus SBRT) in participants with MSS mCRC (Part B)
Eligibility:
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status \<= 1
* Histopathologic confirmation of mCRC by the NCI Laboratory of Pathology (LP)
* Disease not amenable to curative resection
* At least 1 lesion amenable to SBRT and a second lesion outside the radiation field to serve as a target lesion
* Adequate organ and marrow function
Design:
* This is a phase II, single-arm, non-randomized, trial using tiragolumab and atezolizumab in combination with SBRT.
* A maximum of 30 participants with MSS mCRC will be enrolled.
* Participants will receive atezolizumab and tiragolumab intravenously (IV) every 3 weeks (21-day cycles) with SBRT occurring on Days 1, 3, and 5 of Cycle 1 for 2 years.
* Participants will be evaluated routinely for toxicity and will have re-staging imaging every 9 weeks (every 3 cycles).
* Optional research biopsies will be done at baseline and during week 1 of cycle 2. If the participant has disease progression after cycle 3, a post-treatment biopsy may be performed.
* The proportion of participants that are progression-free at 9 weeks will be evaluated as a binary endpoint.
* Metastatic colorectal cancer (mCRC) is incurable for most patients and carries a poor diagnosis.
* Immune-based approaches in solid tumor malignancies have seen much progress but these have limited efficacy for microsatellite stable (MSS) mCRC.
* The Gastrointestinal Malignancies Section at NCI conducted a Pilot Study of the PD-1 Targeting Agent AMP-224 with low-dose cyclophosphamide and stereotactic body radiation therapy (SBRT) that supports potential antitumor efficacy of the combination of immunotherapy and radiation in MSS mCRC (NCT02298946).
* T cell immunoreceptor with Ig and ITIM domains (TIGIT) is an inhibitory receptor expressed in multiple cancers on tumor-infiltrating cytotoxic T cells, helper T cells, natural killer (NK) cells, and regulatory T cells. Its main ligand, CD155, is expressed on tumor-infiltrating myeloid cells and upregulated on cancer cells, contributing to local immune-surveillance suppression.
* Among inhibitory immune checkpoint molecules, a unique property of TIGIT blockade is that it enhances not only anti-tumor effector T-cell responses, but also NK-cell responses, and reduces the suppressive capacity of regulatory T cells.
* Pre-clinical studies show that the co-blockade of TIGIT and the programmed cell death protein 1 (PD-1) / programmed cell death ligand 1 (PD-L1) pathway may lead to decreased tumor volume. Notably, this has been observed in anti-PD-1 resistant tumor models.
* Preclinical and clinical evidence suggests further increased benefit to the double immune checkpoint blockade through increased expression of PD-L1 and neoantigens in response to SBRT.
* Early results from clinical trials suggest clinical activity of anti-TIGITplus anti-PD-L1 in solid tumors and the effect of combining immunotherapy with radiation in heavily pretreated MSS mCRC patients providing a proof of concept that radiation enhances immunotherapy response.
* A combination of anti-PD-L1, anti-TIGIT, and SBRT may increase CRC susceptibility to immune therapy given the promising activity of anti-TIGIT in combination with anti-PDL1 in preclinical studies of mice bearing subcutaneous CT26 colon tumors.
Primary Objectives:
* To confirm the Recommended Phase II dose (RP2D) of the combination therapy (tiragolumab and atezolizumab plus SBRT) in participants with MSS mCRC (Part A)
* To determine the proportion of participants without progression after 9 weeks of the combination therapy (tiragolumab and atezolizumab plus SBRT) in participants with MSS mCRC (Part B)
Eligibility:
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status \<= 1
* Histopathologic confirmation of mCRC by the NCI Laboratory of Pathology (LP)
* Disease not amenable to curative resection
* At least 1 lesion amenable to SBRT and a second lesion outside the radiation field to serve as a target lesion
* Adequate organ and marrow function
Design:
* This is a phase II, single-arm, non-randomized, trial using tiragolumab and atezolizumab in combination with SBRT.
* A maximum of 30 participants with MSS mCRC will be enrolled.
* Participants will receive atezolizumab and tiragolumab intravenously (IV) every 3 weeks (21-day cycles) with SBRT occurring on Days 1, 3, and 5 of Cycle 1 for 2 years.
* Participants will be evaluated routinely for toxicity and will have re-staging imaging every 9 weeks (every 3 cycles).
* Optional research biopsies will be done at baseline and during week 1 of cycle 2. If the participant has disease progression after cycle 3, a post-treatment biopsy may be performed.
* The proportion of participants that are progression-free at 9 weeks will be evaluated as a binary endpoint.
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 001589-C | None | None | View |