What side effects are associated with this type of intervention?

Common side effects of CAR T-cell therapies for colorectal cancer, such as those targeting CEA-expressing, HLA-A*02-negative tumor cells, include cytokine release syndrome (CRS) with symptoms like fever, nausea, headache, and low blood pressure. Neurological toxicities such as confusion and seizures are also frequent. Additionally, patients may experience cytopenias, infections, and fatigue due to the immune system's response to the therapy.

What prior FDA approvals exist?

FDA-approved treatments for colorectal cancer include various chemotherapies, targeted therapies, and immunotherapies. Notably, immunotherapies such as pembrolizumab (Keytruda) and nivolumab (Opdivo) have been approved for microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer. While CAR T-cell therapies have shown promise in hematologic malignancies, their application in solid tumors like colorectal cancer is still under investigation. The A2B530 Tmod CAR T cells, which target CEA-expressing, HLA-A*02-negative tumor cells, represent an innovative approach that is currently being evaluated in clinical trials.

What other types of research exist?

Promising alternatives to A2B530 Tmod CAR T cells for colorectal cancer patients include: 1) Sequential CD22/CD19 CAR-T therapy, which has shown robust antitumor effects in other cancers and may be adapted for CRC. 2) Immune checkpoint inhibitors such as pembrolizumab and nivolumab, which target PD-1/PD-L1 pathways and have shown efficacy in various solid tumors. 3) Novel targeted therapies like FGFR inhibitors (e.g., BGJ398) and other molecularly targeted agents that are being explored for their efficacy in solid tumors, including CRC.

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CAR T-cell Therapy

A2B530 CAR T Therapy for Solid Cancers (EVEREST-1 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

ECOG performance status of 0 to 1

Histologically confirmed recurrent unresectable, locally advanced, or metastatic CRC, NSCLC, PANC, or other solid tumors associated with CEA expression. Measurable disease is required with lesions of >1.0 cm by computed tomography (CT). (Soluble CEA is not acceptable as the sole measure of disease).

Must not have

Females of childbearing potential who are pregnant or breastfeeding

Unstable angina, arrhythmia, myocardial infarction, or any other significant cardiac disease within the last 6 months

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from the time of informed consent until 24 months (2 years) post a2b530 infusion.

Awards & highlights

No Placebo-Only Group

Summary

This trial tests A2B530, a treatment using modified immune cells from the patient, in adults with hard-to-treat cancers like colorectal, pancreatic, and lung cancer. The treatment aims to target and kill cancer cells while protecting healthy cells.

Who is the study for?

This trial is for adults with certain solid tumors like colorectal, pancreatic, or non-small cell lung cancer that express CEA and lack HLA-A*02. They must have a life expectancy of at least 3 months, be able to follow the study plan including long-term safety checks, and have completed necessary prior treatments. Pregnant or breastfeeding individuals are excluded as well as those not using birth control.

What is being tested?

The study tests A2B530 CAR T-cells in patients with specific solid tumors. It's divided into two phases: Phase 1 determines the safest dose; Phase 2 checks if this dose effectively targets tumor cells while sparing healthy ones. Participants will undergo a preconditioning regimen before receiving the A2B530 treatment.

What are the potential side effects?

Potential side effects may include reactions related to immune system activation against cancer cells which can affect normal tissues leading to symptoms such as fever, fatigue, nausea, and potential organ inflammation.

Eligibility Criteria

Inclusion Criteria

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

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I can carry out all my daily activities without help.

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My cancer is advanced, cannot be surgically removed, and shows on scans.

Exclusion Criteria

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

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I am not pregnant or breastfeeding.

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I have not had a heart attack or serious heart issues in the last 6 months.

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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.

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I haven't had cancer treatment within 3 weeks or before A2B530 infusion.

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I need extra oxygen at home.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from the time of informed consent until 24 months (2 years) post a2b530 infusion.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from the time of informed consent until 24 months (2 years) post a2b530 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 a2b530 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 A2B530

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: A2530Experimental Treatment2 Interventions

Patients receive Preconditioning Lymphodepletion (PCLD) Regimen followed by a single dose of A2B530 intravenously on day 0

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

Common treatments for colorectal cancer (CRC) include surgery, chemotherapy, targeted therapy, and immunotherapy. Surgery aims to remove the tumor and surrounding tissues. Chemotherapy uses drugs to kill rapidly dividing cancer cells. Targeted therapies, such as cetuximab and bevacizumab, inhibit specific molecules involved in tumor growth and angiogenesis. Immunotherapy, including CAR T-cell therapy like A2B530, involves modifying a patient's T cells to target and destroy cancer cells expressing specific antigens, such as CEA, while sparing healthy cells. This is particularly important for CRC patients as it offers a more personalized and potentially effective treatment option, especially for those with tumors that have lost HLA-A*02 expression, making them less responsive to traditional therapies.

The Novel Therapeutic Landscape for Relapsed/Refractory Diffuse Large B Cell Lymphoma.