Immunotherapy + Radiation for Colorectal Cancer

Overseen By Maria C Monge Bonilla, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Immunostimulatory agents

Disqualifiers: Curative resection, CNS metastasis, Autoimmune, 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: 7

Duration: 2 years

36 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have had chemotherapy, radiation, or certain other treatments within a few weeks before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Atezolizumab, Tecentriq, Stereotactic Body Radiation Therapy (SBRT), and Tiragolumab for colorectal cancer?

Research suggests that combining immunotherapy with radiation therapy can improve outcomes for gastrointestinal cancers, including colorectal cancer. Additionally, studies have shown that Atezolizumab, when combined with radiation therapy, has shown promising results in other cancers, such as bladder and lung cancer, indicating potential effectiveness in colorectal cancer as well. ^{1 2 3 4 5}

Is the combination of immunotherapy and radiation generally safe for humans?

The combination of immunotherapy drugs like atezolizumab with radiation therapy has been studied in various cancers, such as bladder and lung cancer, and is generally well tolerated. However, immune-related adverse events (side effects due to the immune system's response) can occur, and their management is based on clinical experience. ^{1 3 5 6 7}

How is the treatment with Atezolizumab and Tiragolumab for colorectal cancer different from other treatments?

This treatment is unique because it combines immunotherapy (which helps the immune system fight cancer) with radiation therapy, potentially enhancing the body's ability to attack cancer cells. This combination aims to improve outcomes by using radiation to make cancer cells more vulnerable to immune system attacks, a strategy that is still being researched for its full potential. ^{2 8 9 10 11}

Research Team

Maria C Monge Bonilla, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

This trial is for adults with metastatic colorectal cancer that's microsatellite stable (MSS). Participants must be able to perform normal tasks and provide a tissue sample from their tumor. They will undergo various tests, including blood work, imaging scans, heart function tests, and an assessment of daily activity levels.

Inclusion Criteria

Women of child-bearing potential (WOCBP) must agree to use a highly effective method of contraception (hormonal, intrauterine device [IUD], surgical sterilization, abstinence) at the study entry and up to 5 months after the last dose of the study drugs (restriction period)

Participants must be willing to co-enroll in protocol 11-C-0112, Acquisition of Blood and Tumor Tissue Samples from Patients with Gastrointestinal Cancer

My colorectal cancer diagnosis is confirmed by a lab test or biopsy.

Exclusion Criteria

I haven't taken any antibiotics in the last 2 weeks.

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

My calcium levels are not higher than normal and I don't have symptoms of high calcium.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive tiragolumab and atezolizumab intravenously every 3 weeks with SBRT on Days 1, 3, and 5 of Cycle 1

2 years

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Every 3 months (in-person)

Radiation

Participants receive stereotactic body radiation therapy on Days 1, 3, and 5 of Cycle 1

1 week

Treatment Details

Interventions

• Atezolizumab
• Stereotactic Body Radiation Therapy (SBRT)
• Tiragolumab

Trial Overview The study is testing the combination of two immunotherapy drugs—tiragolumab and atezolizumab—with Stereotactic Body Radiation Therapy (SBRT) in treating MSS mCRC. Patients receive both drugs via IV on day 1 of each 3-week cycle plus radiation therapy on days 1, 3, and 5 of the first cycle.

Participant Groups

Group I: Arm 1 Experimental Treatment 3 Interventions

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

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

The TREASURE trial is a phase II clinical study involving 104 patients with extensive disease small cell lung cancer (SCLC) to evaluate the effectiveness of adding thoracic radiotherapy (TRT) to atezolizumab maintenance therapy after initial chemo-immunotherapy, with overall survival as the primary endpoint.

This trial aims to enhance treatment outcomes by exploring the synergistic effects of combining immunotherapy with radiotherapy, while also assessing safety and collecting biomarker samples for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol of the TREASURE study: Thoracic RadiothErapy with Atezolizumab in Small cell lUng canceR Extensive disease - a randomized, open-label, multicenter phase II trial. Bozorgmehr, F., Christopoulos, P., Chung, I., et al.[2022]

Immunotherapy is a promising new approach in cancer treatment, but its effectiveness can vary widely among patients, even those with tumors that are expected to respond well.

Combining immunotherapy with radiation therapy may enhance treatment outcomes for patients with gastrointestinal cancers, supported by strong preclinical evidence and ongoing research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy and radiation therapy for gastrointestinal malignancies: hope or hype? Badiyan, S., Kaiser, A., Eastman, B., et al.[2023]

In a phase 2 study involving 45 patients with invasive bladder cancer, the combination of radiation therapy and atezolizumab resulted in a high pathologic complete response (pCR) rate of 84.4%, particularly in older patients and those with high PD-L1 expression.

The treatment was associated with acceptable toxicity, with 93.3% of patients experiencing adverse events, mostly mild to moderate, and only 13.3% experiencing grade 3 adverse events, indicating that this approach could be a viable bladder-preserving option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Bladder Preservation Therapy in Combination with Atezolizumab and Radiation Therapy (BPT-ART) for Invasive Bladder Cancer: Interim Analysis from a Multicenter, Open-label, Prospective Phase 2 Trial. Kimura, T., Ishikawa, H., Nagumo, Y., et al.[2023]

In a Phase I trial involving 11 patients with rectal cancer, the combination of bevacizumab, capecitabine, oxaliplatin, and radiation therapy was found to be tolerable, with an acceptable toxicity profile at the recommended Phase II dose.

The treatment showed promising efficacy, with 6 patients demonstrating clinical responses, including 2 achieving a pathologic complete response, indicating potential effectiveness for further investigation in a Phase II trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab, oxaliplatin, and capecitabine with radiation therapy in rectal cancer: Phase I trial results. Czito, BG., Bendell, JC., Willett, CG., et al.[2018]

In a phase I study involving 20 patients with early-stage non-small cell lung cancer, the combination of stereotactic ablative radiotherapy (SABR) and the immune-checkpoint inhibitor atezolizumab was well tolerated, with the maximum tolerated dose established at 1200 mg.

Early efficacy signals were observed, with 17% of patients showing responses after two cycles of atezolizumab before starting SABR, and specific biomarkers indicating T cell activation were found to be predictive of treatment benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial. Monjazeb, AM., Daly, ME., Luxardi, G., et al.[2023]

A 75-year-old man with metastatic melanoma and myasthenia gravis achieved complete and lasting tumor regression after receiving a combination of pembrolizumab (an immune checkpoint inhibitor) and targeted radiotherapy, despite being on immunosuppressive medications.

This case highlights the complex interactions between immunosuppressive therapies and immune checkpoint inhibitors, suggesting that certain patients with autoimmune conditions may still benefit from immuno-radiotherapy combinations, even after mixed responses to previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durable Metastatic Melanoma Remission Following Pembrolizumab and Radiotherapy: A Case Report of Prophylactic Immunosuppression in a Patient with Myasthenia Gravis and Immune-Mediated Colitis. Moradi, LA., Clark, CA., Schneider, CS., et al.[2022]

Immune checkpoint inhibitors, such as pembrolizumab and nivolumab, can lead to immune-related adverse events (irAEs) due to their mechanism of enhancing the immune response against cancer, which can sometimes mistakenly target healthy tissues.

This study reviewed 128 reports involving 239 cases of toxicities associated with these treatments, highlighting the need for careful management of irAEs, as there is currently no standardized approach based on prospective trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of immune checkpoint inhibitor-related adverse events: A review of case reports. Si, X., Song, P., Ni, J., et al.[2021]

Combining radiation therapy with immunotherapy shows great potential for enhancing cancer treatment, as preclinical studies suggest that radiation can make tumor cells more vulnerable to immune attacks.

Clinical trials have begun to support the idea that this combination can effectively boost antitumor immune responses, with ongoing studies exploring various therapeutic vaccines alongside radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining radiation and immunotherapy for synergistic antitumor therapy. Ferrara, TA., Hodge, JW., Gulley, JL.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Protocol of the TREASURE study: Thoracic RadiothErapy with Atezolizumab in Small cell lUng canceR Extensive disease - a randomized, open-label, multicenter phase II trial. [2022]

2. China pubmed.ncbi.nlm.nih.gov

Immunotherapy and radiation therapy for gastrointestinal malignancies: hope or hype? [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Bladder Preservation Therapy in Combination with Atezolizumab and Radiation Therapy (BPT-ART) for Invasive Bladder Cancer: Interim Analysis from a Multicenter, Open-label, Prospective Phase 2 Trial. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Bevacizumab, oxaliplatin, and capecitabine with radiation therapy in rectal cancer: Phase I trial results. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Atezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Durable Metastatic Melanoma Remission Following Pembrolizumab and Radiotherapy: A Case Report of Prophylactic Immunosuppression in a Patient with Myasthenia Gravis and Immune-Mediated Colitis. [2022]

7. Singapore pubmed.ncbi.nlm.nih.gov

Management of immune checkpoint inhibitor-related adverse events: A review of case reports. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Combination of Immunotherapy and Radiation Therapy in Gastrointestinal Cancers: An Appraisal of the Current Literature and Ongoing Research. [2023]

9. China pubmed.ncbi.nlm.nih.gov

Immune blockade inhibitors and the radiation abscopal effect in gastrointestinal cancers. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Can immunostimulatory agents enhance the abscopal effect of radiotherapy? [2022]

11. England pubmed.ncbi.nlm.nih.gov

Combining radiation and immunotherapy for synergistic antitumor therapy. [2021]