What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC) include chemotherapy, radiation therapy, and immunotherapy, including CAR T-cell therapies. Chemotherapy can cause side effects such as fatigue, nausea, vomiting, hair loss, and increased risk of infection. Radiation therapy may lead to skin irritation, fatigue, and damage to nearby organs. Immunotherapy, including CAR T-cell therapies, can cause immune-related side effects such as inflammation in various organs, skin reactions, endocrine issues, and more severe conditions like pneumonitis and colitis. Specific to CAR T-cell therapies, patients may experience cytokine release syndrome (CRS) and neurotoxicity, which require close monitoring and management.

What prior FDA approvals exist?

FDA-approved treatments for Non-Small Cell Lung Cancer (NSCLC) include several targeted and immunotherapy options. Pembrolizumab, an anti-PD-1 therapy, has shown significant improvement in overall survival when combined with chemotherapy in advanced NSCLC. Atezolizumab, another immunotherapy targeting PD-L1, has been approved for previously treated advanced NSCLC. Targeted therapies such as osimertinib for EGFR mutations, crizotinib for ALK rearrangements, and sotorasib for KRAS G12C mutations have also been approved. While CAR T-cell therapies like A2B694 Tmod CAR T cells are still under investigation for solid tumors, including NSCLC, they represent a promising future direction in targeting specific tumor antigens and avoiding healthy cells.

What other types of research exist?

Promising novel alternatives to A2B694 Tmod CAR T cells for NSCLC patients include: 1) Immune checkpoint inhibitors such as pembrolizumab and nivolumab, which target PD-1/PD-L1 pathways and have shown efficacy in NSCLC. 2) Bispecific antibodies, which can simultaneously target two different antigens on cancer cells, enhancing immune response. 3) Personalized cancer vaccines, which are designed to elicit a strong immune response against specific tumor antigens. 4) Other CAR T-cell therapies targeting different antigens or incorporating additional modifications to improve efficacy and safety.

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CAR T-cell Therapy

A2B694 CAR T-Cells for Solid Cancers (EVEREST-2 Trial)

Phase 1 & 2

Recruiting

Research Sponsored by A2 Biotherapeutics Inc.

Eligibility Criteria Checklist

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

Must have

Histologically confirmed recurrent unresectable, locally advanced, or metastatic CRC, NSCLC, PANC, OVCA, MESO, or other solid tumors with MSLN expression. Measurable disease is required with lesions of >1.0 cm by CT.

Received previous required therapy for the appropriate solid tumor disease as described in the protocol

Must not have

History of interstitial lung disease including drug-induced interstitial lung disease and radiation pneumonitis that requires treatment with prolonged steroids or other immune suppressive agents within 1 year

Requires supplemental home oxygen

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from the time of informed consent until 24 months (2 years) post a2b694 infusion

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new immune cell therapy for adults with difficult-to-treat solid tumors. The therapy modifies the patient's own immune cells to target and kill cancer cells while protecting healthy cells. The study aims to find a safe dose and see how well it works.

Who is the study for?

This trial is for adults with certain advanced solid tumors like colorectal, lung, pancreatic, ovarian cancer or mesothelioma. These cancers must express a protein called MSLN and lack HLA-A*02 due to mutation. Participants need measurable disease over 1 cm by CT scan, good organ function, an ECOG status of 0-1 (fully active to restricted in physically strenuous activity), and a life expectancy over 3 months.

What is being tested?

The study tests A2B694 CAR T-cell therapy after patients undergo preconditioning lymphodepletion. Phase 1 determines the safe dosage while Phase 2 checks if this dose effectively targets tumor cells without harming healthy ones. Patients previously enrolled in BASECAMP-1 are given A2B694 at the determined safe dose.

What are the potential side effects?

Potential side effects may include immune reactions leading to inflammation in various organs (like lungs), infusion-related reactions from the CAR T-cells themselves such as fever or chills, fatigue from treatment-induced anemia or other blood cell changes, and 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 is advanced, cannot be surgically removed, and shows MSLN.

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I have completed the necessary treatment for my solid tumor as outlined.

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I can carry out all my daily activities without help.

Exclusion Criteria

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

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I have had lung conditions needing long-term steroids or immune suppressants in the past year.

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I need extra oxygen at home.

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My mesothelioma has spread from the lining of my lungs to my abdomen.

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I am not pregnant or breastfeeding.

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I have had a stem cell transplant from a donor.

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I have had a solid organ transplant.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from the time of informed consent until 24 months (2 years) post a2b694 infusion

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from the time of informed consent until 24 months (2 years) post a2b694 infusion

This trial's timeline: 3 weeks for screening, Varies for treatment, and from the time of informed consent until 24 months (2 years) post a2b694 infusion for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Phase 1: Rate of adverse events and dose limiting toxicities (DLTs) by dose level

Phase 1: Recommended Phase 2 Dose (RP2D)

Phase 2: The Overall Response Rate (ORR) for patients

Secondary study objectives

Cytokine analysis

Persistence of A2B694

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: A2B694Experimental Treatment2 Interventions

Patients receive Preconditioning Lymphodepletion (PCLD) Regimen followed by a single dose of A2B694 intravenously on day 0

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

Common treatments for Non-Small Cell Lung Cancer (NSCLC) include immunotherapies and targeted therapies. Immunotherapies, such as checkpoint inhibitors (e.g., nivolumab, pembrolizumab), work by blocking proteins like PD-1/PD-L1 that cancer cells use to evade the immune system, thereby enhancing the body's ability to attack cancer cells. Targeted therapies, such as tyrosine kinase inhibitors (e.g., erlotinib for EGFR mutations), specifically target genetic mutations or proteins that drive cancer growth. The A2B694 Tmod CAR T cells are an advanced form of immunotherapy engineered to target mesothelin (MSLN)-expressing tumor cells while avoiding cells that lack HLA-A*02, potentially reducing off-target effects and improving efficacy. These treatments are crucial for NSCLC patients as they offer more personalized and effective options, especially for those with specific genetic profiles or who have not responded to conventional therapies.

Immune evasion and current immunotherapy strategies in mycosis fungoides (MF) and Sézary syndrome (SS).Immunotherapy for LELC: Case Report and a Focused Review.Addressing the unmet need in lung cancer: The potential of immuno-oncology.