What is the mechanism of action of this treatment?

The most common treatments for Chordoma include surgery, radiation, and increasingly, immunotherapy using monoclonal antibodies like Tiragolumab and Atezolizumab. These monoclonal antibodies work by targeting specific proteins on cancer cells or immune cells, thereby enhancing the immune system's ability to recognize and destroy cancer cells. This mechanism is crucial for Chordoma patients because the tumor's location and resistance to conventional treatments make it challenging to treat effectively. By boosting the immune response, these therapies offer a promising alternative that could lead to better outcomes for patients with this rare and difficult-to-treat cancer.

What side effects are associated with this type of intervention?

Common side effects of monoclonal antibodies like tiragolumab and atezolizumab, which enhance the immune system's response against cancer cells, include immune-related adverse events. These can affect various organs, leading to conditions such as pneumonitis, colitis, hepatitis, endocrinopathies (e.g., thyroiditis, adrenal insufficiency), and skin reactions. Severe side effects can include grade 3 or 4 toxicities, which may necessitate discontinuation of treatment and administration of corticosteroids or other immunosuppressive agents.

What prior FDA approvals exist?

As of now, there are no specific FDA-approved treatments for Chordoma that are directly analogous to Tiragolumab and Atezolizumab, which are monoclonal antibodies designed to enhance the immune system's response against cancer cells. However, immunotherapy has been a growing area of interest in cancer treatment, with several monoclonal antibodies like Pembrolizumab and Nivolumab being approved for other types of cancers. These drugs work by targeting PD-1/PD-L1 pathways to boost the immune system's ability to fight cancer. The ongoing trial of Tiragolumab and Atezolizumab for SMARCB1 or SMARCA4 deficient tumors represents a similar approach and may provide insights into future treatments for Chordoma.

What other types of research exist?

Promising alternatives to Tiragolumab and Atezolizumab for Chordoma patients include Pembrolizumab (an anti-PD-1 antibody) and Nivolumab (another anti-PD-1 antibody). Both have shown efficacy in various cancers and are being explored in multiple clinical trials. Additionally, combination therapies involving these agents with other immunomodulatory drugs or targeted therapies may offer enhanced benefits.

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Checkpoint Inhibitor

Tiragolumab + Atezolizumab for Solid Tumors

Phase 1 & 2

Recruiting

Led By Mary F Wedekind Malone

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have SMARCB1 (INI1) or SMARCA4 deficient tumors verified through institutional immunohistochemistry (IHC) or molecular confirmation of a pathologic tumor bi-allelic SMARCB1 (INI1) or SMARCA4 loss or mutation from a Clinical Laboratory Improvement Act (CLIA) certified lab with specific disease histologies

Patients must have either measurable or evaluable disease for Part A and either measurable disease per RECIST v1.1 for non-CNS tumors or CNS response criteria for CNS tumors for Part B

Must not have

Patients with active autoimmune disease, active immune deficiency, known active tuberculosis, hepatitis B or C infection, recent Epstein-Barr virus (EBV) infection, history of or active human immunodeficiency virus (HIV), significant cardiovascular disease, recent major surgical procedure, history of specific pulmonary conditions, uncontrolled effusions, uncontrolled infection, prior solid organ transplantation, or inability to comply with safety monitoring requirements

Patients who have undergone allogeneic bone marrow or stem cell transplant

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include reactions related to the immune system such as inflammation of organs, infusion-related reactions like fever or chills, fatigue, digestive issues including nausea or diarrhea, changes in blood counts leading to increased infection risk or bleeding problems.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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My cancer can be measured or seen on tests.

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My kidney, liver, and blood tests meet the required levels.

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My disease has returned, is resistant, or is newly diagnosed with no cure.

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I have never received TIGIT targeting therapy.

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I can take care of myself but may not be able to do heavy physical work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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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.

Select...

I have had a bone marrow or stem cell transplant from a donor.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Frequency of cycle 1 dose limiting toxicities of the combination of tiragolumab and atezolizumab in patients < 12 years

Frequency of cycle 1 dose limiting toxicities of tiragolumab as monotherapy in pediatric patients

Frequency of objective response for the combination of tiragolumab and atezolizumab

Secondary study objectives

Duration of response of the combination therapy for tiragolumab and atezolizumab

Overall survival (OS) of the combination therapy for tiragolumab and atezolizumab

Combined Modality Therapy

+3 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Part A (atezolizumab, tiragolumab)Experimental Treatment8 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 blood sample collection on study.

Group II: Arm B (atezolizumab, tiragolumab)Experimental Treatment8 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 blood sample collection on study.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Magnetic Resonance Imaging

2017

Completed Phase 3

~1180

Computed Tomography

2017

Completed Phase 2

~2790

Biospecimen Collection

2004

Completed Phase 3

~2030

Atezolizumab

2016

Completed Phase 3

~5860

Positron Emission Tomography

2011

Completed Phase 2

~2200

Tiragolumab

2019

Completed Phase 3

~2330

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Chordoma include surgery, radiation, and increasingly, immunotherapy using monoclonal antibodies like Tiragolumab and Atezolizumab. These monoclonal antibodies work by targeting specific proteins on cancer cells or immune cells, thereby enhancing the immune system's ability to recognize and destroy cancer cells. This mechanism is crucial for Chordoma patients because the tumor's location and resistance to conventional treatments make it challenging to treat effectively. By boosting the immune response, these therapies offer a promising alternative that could lead to better outcomes for patients with this rare and difficult-to-treat cancer.

Phase 2 study of pembrolizumab in patients with recurrent and residual high-grade meningiomas.Recurrent glioma clinical trial, CheckMate-143: the game is not over yet.