What side effects are associated with this type of intervention?

Common treatments for NSCLC, particularly those involving immune checkpoint inhibitors like Anti-PD1 (e.g., Zimberelimab), often result in immune-related adverse events. These can include skin reactions, endocrine disorders, pneumonitis, and colitis. Anti-TIGIT and A2R antagonists, while still under investigation, may have similar immune-related side effects. Chemotherapy, often used in combination with these immunotherapies, typically causes neutropenia, febrile neutropenia, anemia, and gastrointestinal issues. The combination of these treatments can lead to a higher incidence of severe adverse events, including pneumonia, diarrhea, and acute kidney injury.

What prior FDA approvals exist?

The FDA has approved several immunotherapies for the treatment of Non-Small Cell Lung Cancer (NSCLC). Pembrolizumab (Keytruda), an anti-PD1 therapy, has been approved for use in combination with chemotherapy for patients with advanced NSCLC, regardless of PD-L1 expression. Nivolumab (Opdivo), another anti-PD1 therapy, is approved for previously treated advanced NSCLC. Atezolizumab (Tecentriq), an anti-PD-L1 therapy, has been approved in combination with chemotherapy for first-line treatment of metastatic NSCLC. While anti-TIGIT and A2R antagonist therapies are still under investigation, these approvals highlight the growing role of immunotherapy in NSCLC treatment.

What other types of research exist?

Promising novel alternatives for NSCLC patients include: 1) Sintilimab plus Anlotinib, which has shown encouraging efficacy, durability, and safety as a chemotherapy-free regimen. 2) Pembrolizumab-containing chemo-immunotherapy combinations, which are currently the standard treatment in clinical practice for naïve advanced NSCLC patients. 3) Nivolumab plus Ipilimumab plus short-course chemotherapy, which offers a reduced rate of severe treatment-related adverse events and limited chemotherapy administration.

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A2R Antagonist

Triple Combination Immunotherapy for Lung Cancer

Phase 2

Waitlist Available

Led By Daniel Morgensztern, M.D.

Research Sponsored by Washington University School of Medicine

Eligibility Criteria Checklist

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

Must have

Documented PD-L1 expression of at least 1% by a US FDA-approved PD-L1 assay or using the clone 22C3 antibody from archival biopsy or fresh tumor tissue

At least 18 years of age

Must not have

Any active autoimmune disease or documented history of autoimmune disease or syndrome that required systemic treatment in the past 2 years

Due to the potential risk for drug-drug interactions with etrumadenant, participants must not have had:

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through completion of follow-up (estimated to be 5 years)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of three drugs to help the immune system fight lung cancer. The drugs are zimberelimab, domvanalimab, and etrumadenant. They are being tested on patients who have already tried other immune-based treatments. The goal is to see if this new combination can work better.

Who is the study for?

This trial is for adults with non-small cell lung cancer who've had previous treatments including immune checkpoint blockers. They must have at least one measurable tumor and cannot have more than two prior therapies in the metastatic setting. Participants need normal organ function, no severe psychiatric issues or substance abuse, not be pregnant/breastfeeding, and can't have certain other cancers or active autoimmune diseases.

What is being tested?

The study tests a combination of three drugs: Zimberelimab, Domvanalimab, and Etrumadenant on patients with non-small cell lung cancer who didn't respond well to previous treatments. It explores how these drugs work together since they target different aspects of the immune system's ability to fight cancer.

What are the potential side effects?

Potential side effects may include typical reactions related to immune-based cancer therapies such as fatigue, skin reactions, inflammation in various organs (like lungs or intestines), hormonal gland problems (like thyroid dysfunction), infusion-related reactions and possible increased risk of infections.

Eligibility Criteria

Inclusion Criteria

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

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My cancer shows PD-L1 expression of 1% or more.

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I am 18 years old or older.

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I've had 1-2 treatments for my cancer, including an immune therapy.

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My lung cancer is confirmed to be advanced and of a specific type.

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I am fully active and can carry on all my pre-disease activities without restriction.

Exclusion Criteria

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

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I have not needed treatment for an autoimmune disease in the last 2 years.

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I have not taken any medication that could interact with etrumadenant.

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My cancer does not have EGFR, ALK, ROS1, or RET mutations.

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I can take medications by mouth without any issues.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through completion of follow-up (estimated to be 5 years)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through completion of follow-up (estimated to be 5 years)

This trial's timeline: 3 weeks for screening, Varies for treatment, and through completion of follow-up (estimated to be 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

Objective response rate (ORR)

Secondary study objectives

Disease control rate (DCR)

Duration of response (DoR)

Number of discontinuations due to treatment-related adverse events

+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: Cohort B: Zimberelimab + Domvanalimab + EtrumadenantExperimental Treatment3 Interventions

* Patients will be treated on 21-day cycles with 360 mg zimberelimab intravenously on Day 1, 15 mg/kg domvanalimab intravenously on Day 1, and 150 mg etrumadenant orally daily on Days 1 to 21. * Cohort B participants are those that have PD-L1 ≥ 50%.

Group II: Cohort A: Zimberelimab + Domvanalimab + EtrumadenantExperimental Treatment3 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Zimberelimab

2020

Completed Phase 2

~230

Etrumadenant

2018

Completed Phase 2

~300

0 / 9Eligibility 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 Non-Small Cell Lung Cancer (NSCLC) often involve immunotherapies that target specific pathways to enhance the body's immune response against cancer cells. Zimberelimab (Anti-PD1) blocks the PD-1 receptor on T-cells, preventing cancer cells from evading immune detection. Domvanalimab (Anti-TIGIT) inhibits the TIGIT pathway, which can suppress T-cell activity, thereby boosting the immune response. Etrumadenant (A2R Antagonist) blocks adenosine receptors that can inhibit immune cell function in the tumor microenvironment. These mechanisms are crucial for NSCLC patients as they help to reactivate the immune system to recognize and destroy cancer cells, potentially leading to better treatment outcomes.