Immunotherapy + Radiation for Colorectal Cancer

Overseen By Tim F Greten, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for metastatic colorectal cancer, which has spread beyond the colon and rectum. The trial combines two drugs, tiragolumab and atezolizumab (an immunotherapy drug also known as Tecentriq), with radiation therapy to determine if they work better together than existing options for this cancer type. It specifically targets those with microsatellite stable (MSS) cancer, which typically doesn't respond well to immune-based treatments. Individuals with MSS metastatic colorectal cancer who have tried at least two other treatments without success might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that combining atezolizumab and tiragolumab with radiation therapy has been studied for safety. In these studies, some patients experienced side effects, but they were usually manageable. Common side effects included fatigue, skin reactions, and changes in appetite. No major safety concerns emerged that would prevent these treatments from being used together.

Atezolizumab has already received FDA approval for other uses, indicating its general safety. Tiragolumab remains under study, but early research suggests it is well-tolerated. The combination with radiation therapy is being tested to determine if it offers additional benefits without excessive risk. Overall, the treatment appears safe for most people, but monitoring during the trial is crucial to identify any issues early. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of atezolizumab and tiragolumab for colorectal cancer because these treatments harness the power of the immune system in a novel way. Unlike traditional chemotherapy, which directly attacks cancer cells, atezolizumab is an immune checkpoint inhibitor that helps the immune system recognize and fight cancer cells. Tiragolumab works alongside atezolizumab by targeting a different checkpoint pathway, potentially enhancing the immune response even further. This dual action aims to provide a more robust and sustained attack on cancer cells, offering hope for better outcomes in patients with colorectal cancer.

What evidence suggests that this treatment might be an effective treatment for metastatic colorectal cancer?

Research shows that atezolizumab, a type of immunotherapy, can help treat various cancers by enabling the immune system to attack cancer cells. Studies have also examined tiragolumab, a drug that targets a specific mechanism tumors use to evade the immune system. In this trial, participants will receive a combination of atezolizumab and tiragolumab, along with stereotactic body radiation therapy (SBRT), a precise form of radiation therapy. Although specific results for colorectal cancer are still under investigation, this combination aims to assist patients with microsatellite stable (MSS) metastatic colorectal cancer, who typically do not respond well to current immunotherapies. Early results in other cancers suggest potential benefits, making this approach worth exploring. ^{2 3 4 5 6}

Who Is on the Research Team?

Tim F Greten, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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]

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]

Citations

1. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-08057

Immunotherapies in Combination With Stereotactic Body ... Objective: To test 2 drugs (tiragolumab and atezolizumab) combined with radiation therapy in people with MSS mCRC. Eligibility: People aged 18 years and older ...

2. clinicalstudies.info.nih.gov clinicalstudies.info.nih.gov/protocoldetails.aspx?id=001589-C&&query=0

NIH Clinical Center: Search the Studies A Phase II Study of Immunotherapies (Tiragolumab and Atezolizumab) in Combination with Stereotactic Body Radiation Radiotherapy in Microsatellite Stable (MSS) ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37946136/

A phase I study of the combination of atezolizumab, ... We aim to assess the combination of tiragolumab with atezolizumab and SBRT in metastatic, previously treated by ICIs, non-small cell lung cancer, head and neck ...

4. researchgate.net researchgate.net/publication/375522590_A_phase_I_study_of_the_combination_of_atezolizumab_tiragolumab_and_stereotactic_body_radiation_therapy_in_patients_with_metastatic_multiorgan_cancer

(PDF) A phase I study of the combination of atezolizumab ... We aim to assess the combination of tiragolumab with atezolizumab and SBRT in metastatic, previously treated by ICIs, non-small cell lung cancer, head and neck ...

5. 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.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05259319

NCT05259319 | Study Evaluating the Safety and ... This study (phase I clinical trial and expansion cohorts) will evaluate safety and efficacy of combination of atezolizumab and tiragolumab, with concomitant ...