Tiragolumab + Atezolizumab for Solid Tumors

Recruiting at 38 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Systemic steroids, Immunosuppressants

Disqualifiers: Pregnancy, Active autoimmune, Hepatitis, 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: 21

Duration: Up to 5 years

86 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before enrolling. You must not be on systemic steroid medications, other anti-cancer agents, or systemic immunosuppressive medications during the study. If you are on these medications, you need to stop them at least 14 days before enrolling.

What data supports the effectiveness of the drug combination Tiragolumab and Atezolizumab for solid tumors?

Research shows that Tiragolumab, when combined with Atezolizumab, has shown promising results in treating solid cancers, especially non-small cell lung cancer. Atezolizumab alone has been effective in treating advanced bladder cancer, with significant tumor responses and improved survival rates. ^{1 2 3 4 5}

Is the combination of Tiragolumab and Atezolizumab safe for humans?

Atezolizumab, used alone or in combination with other treatments, has been studied in various cancers and generally shows an acceptable safety profile. Common side effects include fatigue, decreased appetite, and nausea, while more serious effects can include lung inflammation and liver issues. Tiragolumab, when combined with Atezolizumab, has shown promising results in trials, but specific safety data for this combination is limited. ^{1 2 6 7 8}

What makes the drug combination of Tiragolumab and Atezolizumab unique for treating solid tumors?

The combination of Tiragolumab and Atezolizumab is unique because it targets two different immune checkpoints, TIGIT and PD-L1, which may enhance the immune system's ability to fight solid tumors more effectively than targeting PD-L1 alone. This dual approach has shown promising results, particularly in non-small cell lung cancer, by potentially improving patient outcomes compared to existing treatments. ^{1 2 9 10 11}

What is the purpose of this trial?

This trial studies how well tiragolumab and atezolizumab work in children and adults with difficult-to-treat tumors missing specific genes. These treatments help the immune system attack cancer and stop it from growing. Atezolizumab is an antibody that has been used with other treatments for various cancers.

Research Team

Mary F. Wedekind Malone

Principal Investigator

Pediatric Early Phase Clinical Trial Network

Eligibility Criteria

This trial is for children and adults with specific aggressive cancers that lack SMARCB1 or SMARCA4 genes. Participants must have recovered from previous cancer treatments, not received certain therapies recently, and have measurable disease. It's open to those aged 12 months and older (under 18 for part A; no upper age limit for part B), who haven't had TIGIT therapy, are not on systemic steroids, and meet blood count and organ function criteria.

Inclusion Criteria

My tumor lacks SMARCB1 (INI1) or SMARCA4, confirmed by a certified lab test.

I have recovered from side effects of previous cancer treatments.

I haven't had certain medications or live vaccines in the last 30 days.

Exclusion Criteria

I do not have any active autoimmune diseases, infections like TB, hepatitis B or C, recent EBV, HIV, serious heart issues, recent major surgeries, specific lung conditions, uncontrolled effusions or infections, prior organ transplants, and can follow safety monitoring.

Pregnant or breast-feeding women

You are allergic to certain ingredients.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive tiragolumab and atezolizumab intravenously every 21 days for up to 5 years, with imaging scans and blood sample collection

Up to 5 years

Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion at months 3, 6, 9, 12, 18, 24, 36, 48, and 60

Up to 5 years

Follow-up visits at specified months

Treatment Details

Interventions

• Atezolizumab
• Tiragolumab

Trial Overview The trial tests tiragolumab plus atezolizumab in patients with relapsed or refractory tumors lacking the SMARCB1/SMARCA4 genes. This study aims to see if these immunotherapy drugs can help the immune system fight cancer more effectively by preventing tumor growth.

Participant Groups

Group I: Part A (atezolizumab, tiragolumab) Experimental Treatment 9 Interventions

Patients receive tiragolumab IV over 30-90 minutes on day 1 of each cycle and atezolizumab IV over 30-60 minutes on day 1 of each cycle starting in cycle 2. Treatment repeats every 21 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients undergo standard imaging scans including x-rays, CT, MRI, and/or FDG PET-CT, throughout the trial. Patients also undergo ECHO during screening and blood sample collection on study.

Group II: Arm B (atezolizumab, tiragolumab) Experimental Treatment 8 Interventions

Patients receive atezolizumab IV over 30-60 minutes on day 1 and tiragolumab IV over 30-90 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients also undergo standard imaging scans including x-rays, CT, MRI, and/or FDG PET-CT throughout the trial. Patients also undergo ECHO during screening and blood sample collection on study.

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

Tiragolumab, a TIGIT inhibitor, shows promise in treating solid cancers, particularly non-small cell lung cancer, based on results from phase I and II trials.

The combination of tiragolumab with the PD-L1 inhibitor atezolizumab has demonstrated statistically significant efficacy in multiple solid tumors, suggesting a potential new treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tiragolumab Impresses in Multiple Trials. [2021]

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, S., et al.[2022]

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

Atezolizumab, an anti-PD-L1 therapy, showed long-term safety and efficacy in patients with metastatic urothelial carcinoma, with a median follow-up of 37.8 months and a low incidence of severe treatment-related adverse events (9%).

The treatment resulted in a 26% objective response rate, with a median duration of response of 22.1 months, and median overall survival of 10.1 months, particularly benefiting patients with higher PD-L1 expression on immune cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab (MPDL3280A) Monotherapy for Patients With Metastatic Urothelial Cancer: Long-term Outcomes From a Phase 1 Study. Petrylak, DP., Powles, T., Bellmunt, J., et al.[2022]

Atezolizumab combined with chemotherapy showed promising efficacy in treating advanced, treatment-naïve non-small-cell lung cancer (NSCLC), with overall response rates of 36% to 68% across different chemotherapy regimens in a study of 76 patients.

The treatment was generally well tolerated, although common severe side effects included neutropenia and anemia, indicating a manageable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival follow-up of atezolizumab in combination with platinum-based doublet chemotherapy in patients with advanced non-small-cell lung cancer. Liu, SV., Camidge, DR., Gettinger, SN., et al.[2022]

Atezolizumab, the first anti-PD-L1 monoclonal antibody approved by the FDA, has shown promising efficacy in treating metastatic triple-negative breast cancer, supported by data from the Phase III IMpassion130 trial.

The review highlights the pharmacodynamic and pharmacokinetic properties of atezolizumab, emphasizing its safety and effectiveness in various cancers, including small-cell lung cancer and renal cell cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. Mavratzas, A., Seitz, J., Smetanay, K., et al.[2020]

Atezolizumab significantly improves overall survival in patients with metastatic non-small cell lung cancer (mNSCLC), with median survival times of 13.8 months in the atezolizumab group compared to 9.6 months in the docetaxel group in the OAK trial.

The treatment has an acceptable safety profile, with common side effects including fatigue and decreased appetite, and serious immune-related adverse events occurring in a small percentage of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. Weinstock, C., Khozin, S., Suzman, D., 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]

In the phase III IMagyn050 trial involving patients with newly diagnosed ovarian cancer, the addition of atezolizumab to standard chemotherapy did not improve progression-free survival (PFS) in patients with BRCA1/2 mutations or homologous recombination deficiency (HRD).

Despite the presence of BRCA1/2 mutations or HRD, most ovarian tumors exhibited low tumor mutation burden (TMB), indicating that genomic instability does not predict enhanced sensitivity to immune checkpoint inhibitors like atezolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of Genomic Landscape on Cancer Immunotherapy for Newly Diagnosed Ovarian Cancer: Biomarker Analyses from the IMagyn050 Randomized Clinical Trial. Landen, CN., Molinero, L., Hamidi, H., et al.[2023]

In the phase III SKYSCRAPER-02 study involving 490 patients with untreated extensive-stage small-cell lung cancer, the addition of tiragolumab to atezolizumab and chemotherapy did not significantly improve progression-free survival (PFS) or overall survival (OS).

The combination treatment was well tolerated, with similar rates of immune-mediated adverse events between the tiragolumab and control groups, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SKYSCRAPER-02: Tiragolumab in Combination With Atezolizumab Plus Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer. Rudin, CM., Liu, SV., Soo, RA., et al.[2023]

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]

References

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

Tiragolumab Impresses in Multiple Trials. [2021]

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

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. [2019]

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

Atezolizumab (MPDL3280A) Monotherapy for Patients With Metastatic Urothelial Cancer: Long-term Outcomes From a Phase 1 Study. [2022]

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

Long-term survival follow-up of atezolizumab in combination with platinum-based doublet chemotherapy in patients with advanced non-small-cell lung cancer. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. [2020]

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

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. [2022]

8. 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]

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

Influence of Genomic Landscape on Cancer Immunotherapy for Newly Diagnosed Ovarian Cancer: Biomarker Analyses from the IMagyn050 Randomized Clinical Trial. [2023]

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

SKYSCRAPER-02: Tiragolumab in Combination With Atezolizumab Plus Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer. [2023]

11. 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]