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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and effectiveness of a combination of three treatments—atezolizumab (an immunotherapy drug), tiragolumab (an immunotherapy drug), and a special type of radiation therapy—for individuals with advanced cancers that have spread and cannot be surgically removed. The study aims to determine if this combination can control or reduce tumors. It suits those with solid cancers that have spread and lack other effective treatment options. Participants may have tried other treatments before, and prior exposure to certain immune therapies is acceptable. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this novel combination therapy.

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.

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

Research has shown that the combination of tiragolumab and atezolizumab is generally well-tolerated. Studies have found no new safety issues compared to using atezolizumab alone. In trials, patients managed the combination well, with no significant increase in severe side effects.

For the atezolizumab and radiation combination, findings suggest that this pairing is also manageable. Some patients experienced serious but not life-threatening side effects, but these were limited. Overall, this combination appears to have a manageable safety profile.

In summary, both treatment combinations—tiragolumab with atezolizumab, and atezolizumab with radiation—have demonstrated relative safety in previous studies. Participants generally handled them well, with no unusual safety concerns reported. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine two powerful immunotherapy drugs, atezolizumab and tiragolumab, with innovative radiation techniques to enhance the body's immune response against cancer. Unlike traditional chemotherapy or standalone radiation, which directly target cancer cells, this combination aims to boost the immune system's natural ability to fight tumors. Atezolizumab is an immune checkpoint inhibitor that blocks the PD-L1 protein, helping immune cells attack cancer more effectively. Tiragolumab targets a different checkpoint, TIGIT, potentially offering a complementary mechanism to further unleash the immune system. This dual-action approach, paired with radiation, could offer a more robust and sustained attack on cancer cells compared to conventional therapies.

What evidence suggests that this trial's treatments could be effective for metastatic solid malignancies?

Research has shown that combining tiragolumab with atezolizumab holds promise for cancer treatment. Participants in this trial may receive this combination, which has proven more effective than past treatments. Specifically, studies have shown that 47.7% of patients experienced a major reduction or disappearance of their tumors.

Another treatment arm in this trial uses atezolizumab with radiation. This combination has also effectively shrunk tumors and improved survival rates. For example, one study found that tumors shrank by an average of 70.2% for some patients. Overall, these treatments offer potential benefits for patients with advanced solid cancers. ^{1 6 7 8 9}

Who Is on the Research Team?

Ecaterina Dumbrava, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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.

Patients must have measurable disease per the RECIST v1.1

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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]

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]

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]

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 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]

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]

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]

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]

Citations

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Effectiveness of Atezolizumab in Addition to Chemotherapy in ... Overall, 1-year, 2-year and 3-year cumulative survival rates were 51.5%, 21.7%, and 12.7%, respectively. Table 4. Evaluation of patients ...

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Timing matters when adding immunotherapy to ... After one year, overall survival for patients receiving chemoradiation alone was 82.6%, compared to 80.2% with concurrent chemoradiation and ...

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First-Line Atezolizumab plus Chemotherapy in Extensive- ... Despite response rates of 60 to 65%, limited progress has been made in more than two decades; outcomes remain poor, with a median overall ...

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safety, clinical activity and ctDNA responses—the ComIT‐1 ... We found the combined treatment to be safe with grade 3 toxicity reported in three patients. As the best overall response, four patients had a partial response.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.4588

Efficacy and safety of atezolizumab concurrent with ... Interim results suggest that ATZ combined with EBRT is a feasible and effective treatment in terms of pCR, with a manageable safety profile.

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NRG Oncology Trial Implies the Addition of Atezolizumab ... The addition of the cancer immunotherapy drug atezolizumab to the standard of care concurrent chemoradiation (cCRT) did not improve overall survival for ...

9. cancernetwork.com cancernetwork.com/view/atezolizumab-plus-chemo-safe-efficacious-in-broader-es-sclc-population

Atezolizumab Plus Chemo Is Safe, Efficacious in Broader ... In the 14 patients treated with thoracic radiotherapy, the median OS was 19.3 months (95% CI, 13.7-not reached), and in the 10 patients who had ...