Tiragolumab + Atezolizumab + Radiation for Cancer

Overseen By Ecaterina Dumbrava, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Immunostimulants

Disqualifiers: Autoimmune disease, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Phase I/Ib

56 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that patients must not have received certain cancer treatments or systemic immunosuppressive medications shortly before starting the trial. It's best to discuss your specific medications with the trial team to see if any adjustments are needed.

What data supports the effectiveness of the treatment Tiragolumab + Atezolizumab + Radiation for Cancer?

Research shows that combining atezolizumab, an immune therapy drug, with radiation therapy can improve outcomes in various cancers, like bladder and lung cancer. Additionally, adding tiragolumab to atezolizumab has shown improved results in non-small cell lung cancer, suggesting potential benefits of this combination. ^{1 2 3 4 5}

Is the combination of Tiragolumab, Atezolizumab, and Radiation generally safe for humans?

Atezolizumab combined with radiation therapy has been studied for safety in various trials, showing that while it can be effective, it may also lead to immune-related side effects. These side effects can include immune system reactions, which are important to monitor during treatment. ^{1 6 7 8 9}

How is the treatment with Tiragolumab, Atezolizumab, and Radiation different from other cancer treatments?

This treatment is unique because it combines two immune checkpoint inhibitors, tiragolumab and atezolizumab, with radiation therapy to potentially enhance the immune response against cancer. This combination aims to improve outcomes by targeting different pathways in the immune system, which is not commonly done in standard treatments. ^{1 2 3 4 5}

What is the purpose of this trial?

An open-label, Phase I/Ib study investigating the safety and efficacy of tiragolumab + atezolizumab + RadScopal™ XRT in patients with metastatic solid malignancies.

Research Team

Ecaterina Dumbrava, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

The TIGER trial is for patients with advanced solid tumors that have spread (metastatic). Participants should meet specific health criteria and not have conditions that could interfere with the study or pose a risk.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

My doctor thinks standard treatments won't work as well for me as this trial might.

Patients must have measurable disease per the RECIST v1.1

Exclusion Criteria

I haven't taken any immune-boosting drugs in the last 4 weeks.

Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tiragolumab, atezolizumab, and RadScopal™ XRT

Phase I/Ib

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• Atezolizumab
• Radiation Therapy
• Tiragolumab

Trial Overview This trial tests the combination of two immunotherapy drugs, Tiragolumab and Atezolizumab, along with RadScopal radiation therapy to see if they are safe and effective in treating metastatic solid malignancies.

Participant Groups

Group I: PhIbP2ArmC Tiragolumab + Atezolizumab Experimental Treatment 2 Interventions

Participants will be randomized to the trial using the Clinical Trial Conduct website

Group II: PhIbP2ArmB Tiragolumab + Atezolizumab + RadScopal XRT Experimental Treatment 3 Interventions

Participants will be randomized to the trial using the Clinical Trial Conduct website

Group III: PhIbP2ArmA Atezolizumab + RadScopal XRT Experimental Treatment 2 Interventions

Participants will be randomized to the trial using the Clinical Trial Conduct website

Group IV: PhI/PhIbP1 Tiragolumab + Atezolizumab + RadScopal XRT Experimental Treatment 3 Interventions

Participants will be randomized to the trial using the Clinical Trial Conduct website

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

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]

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]

This phase I clinical trial is investigating the safety and efficacy of combining the anti-TIGIT monoclonal antibody tiragolumab with the PD-L1 inhibitor atezolizumab and Stereotactic Body Radiation Therapy (SBRT) in patients with metastatic non-small cell lung cancer and other cancers previously treated with immune checkpoint inhibitors.

The primary goal of the trial is to assess the safety of this combination treatment and to evaluate its effectiveness in improving 6-month progression-free survival (PFS), with the study including multiple cancer types and a focus on immune biomarker assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of the combination of atezolizumab, tiragolumab, and stereotactic body radiation therapy in patients with metastatic multiorgan cancer. Roussot, N., Fumet, JD., Limagne, E., et al.[2023]

In a pilot study involving 12 patients with metastatic non-small cell lung cancer, the combination of hypofractionated image-guided radiation therapy (HIGRT) and atezolizumab achieved a disease control rate of 50%, with a partial response in 3 patients.

The treatment was associated with a median overall survival of 6.9 months and a median progression-free survival of 2.3 months, with the incidence of grade 3 adverse events being similar to that of atezolizumab alone, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Study of Atezolizumab Plus Hypofractionated Image Guided Radiation Therapy for the Treatment of Advanced Non-Small Cell Lung Cancer. Qin, A., Rengan, R., Lee, S., et al.[2021]

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]

In a study of 133 patients with metastatic cancers receiving immune checkpoint inhibitors and radiation, 34.6% experienced immune-related adverse events (ir-AEs), with higher rates observed in those receiving both CTLA-4 and PD-1 inhibitors (71% vs 29%).

The combination of palliative radiation and immune checkpoint inhibitors was generally well tolerated, with most ir-AEs being mild, suggesting that this treatment approach can be safely integrated in clinical practice for patients needing both therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter Evaluation of the Tolerability of Combined Treatment With PD-1 and CTLA-4 Immune Checkpoint Inhibitors and Palliative Radiation Therapy. Bang, A., Wilhite, TJ., Pike, LRG., et al.[2022]

A 74-year-old woman with lung adenocarcinoma developed fatal immune thrombocytopenia after receiving pembrolizumab following radiotherapy, highlighting a potential risk of severe immune-related adverse events (irAEs) when combining these treatments.

Flow cytometry analysis showed increased PD-1 and Ki-67 expression in T cells post-radiotherapy, suggesting that radiotherapy may enhance immune activation and contribute to the development of irAEs in patients undergoing anti-PD-1 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab-related Immune Thrombocytopenia in a Patient with Lung Adenocarcinoma Treated by Radiotherapy: Potential Immune-related Adverse Event Elicited by Radiation Therapy. Tamanoi, D., Saruwatari, K., Imamura, K., et al.[2022]

In a study of 60 patients receiving combined immunotherapy and thoracic radiation therapy (iRT), no patients experienced severe grade ≥4 toxicities, indicating a favorable safety profile for this treatment approach.

While some patients did experience grade 3 toxicities, particularly pulmonary and hematologic issues, the overall short-term safety of iRT suggests it can be administered without significant risk of severe adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Combined Immunotherapy and Thoracic Radiation Therapy: Analysis of 3 Single-Institutional Phase I/II Trials. Verma, V., Cushman, TR., Selek, U., et al.[2022]

Atezolizumab significantly improved overall survival in patients with previously treated non-small-cell lung cancer compared to docetaxel, with median survival times of 13.8 months versus 9.6 months, respectively.

The safety profile of atezolizumab was favorable, with only 15% of patients experiencing grade 3 or 4 adverse events, compared to 43% in the docetaxel group, indicating it may be a safer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Rittmeyer, A., Barlesi, F., Waterkamp, D., et al.[2022]

References

1. 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]

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

A phase I study of the combination of atezolizumab, tiragolumab, and stereotactic body radiation therapy in patients with metastatic multiorgan cancer. [2023]

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

A Pilot Study of Atezolizumab Plus Hypofractionated Image Guided Radiation Therapy for the Treatment of Advanced Non-Small Cell Lung Cancer. [2021]

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

Multicenter Evaluation of the Tolerability of Combined Treatment With PD-1 and CTLA-4 Immune Checkpoint Inhibitors and Palliative Radiation Therapy. [2022]

7. Japan pubmed.ncbi.nlm.nih.gov

Pembrolizumab-related Immune Thrombocytopenia in a Patient with Lung Adenocarcinoma Treated by Radiotherapy: Potential Immune-related Adverse Event Elicited by Radiation Therapy. [2022]

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

Safety of Combined Immunotherapy and Thoracic Radiation Therapy: Analysis of 3 Single-Institutional Phase I/II Trials. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. [2022]