A2B395 CAR T-Cell Therapy for Colorectal Cancer

(DENALI-1 Trial)

Recruiting at 13 trial locations

Overseen By Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: A2 Biotherapeutics Inc.

Disqualifiers: Prior transplants, Recent cancer therapy, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

240 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called A2B395, a type of CAR T-cell therapy designed to target and kill cancer cells while sparing healthy ones. It focuses on individuals with certain solid tumors, including colorectal, lung, head and neck, aggressive breast, and kidney cancers. In Phase 1, the trial aims to determine the safest dose of A2B395, and in Phase 2, it will assess whether this dose effectively fights cancer. Participants should have tumors that express a specific protein called EGFR and have already tried other treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications, but it does mention that you should not have had cancer therapy within 3 weeks or 3 half-lives of the A2B395 infusion, and no radiotherapy within 28 days of the infusion. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that A2B395 CAR T-cell therapy is likely to be safe for humans?

An earlier study on A2B395 CAR T-cell therapy showed promising safety results for patients with solid tumors. The research found that most patients tolerated the treatment well. Some experienced side effects, but these were usually mild to moderate, with serious side effects being less common. Researchers continue to test this therapy to determine the safest dose and optimal usage. As this study is in its early stages, safety information is still being gathered. However, these initial findings suggest that A2B395 could be a safe option for treating certain cancers, including colorectal cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for colorectal cancer?

Most treatments for colorectal cancer, like chemotherapy and radiation, work by attacking rapidly dividing cells, which can affect both cancerous and healthy cells. But A2B395 is different because it uses a novel approach called CAR T-cell therapy. This treatment involves modifying a patient's own immune cells to specifically target and destroy cancer cells, potentially leading to more precise and effective cancer eradication. Researchers are excited about A2B395 because it represents a promising shift towards personalized medicine, potentially offering a treatment with fewer side effects and a higher specificity for cancer cells compared to traditional options.

What evidence suggests that A2B395 CAR T-cell therapy might be an effective treatment for colorectal cancer?

Research has shown that A2B395, a type of CAR T-cell therapy under study in this trial, may help treat solid tumors such as colorectal cancer. Studies have found that these specially engineered T cells can effectively locate and attack cancer cells. Early results revealed that some patients experienced tumor shrinkage or complete disappearance. This therapy targets cancer cells while preserving healthy cells, a crucial aspect of cancer treatment. Although further research is necessary, these early findings offer promise for those considering participation in this trial. ^{1 2 5 6 7}

Who Is on the Research Team?

John Welch, MD, PhD

Principal Investigator

A2 Biotherapeutics

Are You a Good Fit for This Trial?

This trial is for people with certain solid tumors (like colorectal, lung, breast, kidney cancers) that have a specific protein called EGFR and lack another marker known as HLA-A*02. Details on who can join are not fully provided but typically include meeting health standards and having the type of cancer being studied.

Inclusion Criteria

Life expectancy of ≥3 months

Willing to comply with study schedule of assessments including long-term safety follow-up

I am fully active or can carry out light work.

Exclusion Criteria

I haven't had cancer treatment within 3 weeks or before A2B395 infusion.

My condition can be treated with standard therapy aimed at curing, not just easing symptoms.

I have had a solid organ transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preconditioning Lymphodepletion (PCLD)

Participants receive a preconditioning lymphodepletion regimen before the main treatment

1 week

Treatment

Participants receive a single dose of A2B395 intravenously

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• A2B395

Trial Overview The study tests A2B395, an experimental CAR T-cell therapy designed to target cancer cells in patients with specific tumor types. It includes two phases: finding a safe dose (Phase 1) and seeing if this dose can effectively kill tumor cells while sparing healthy ones (Phase 2).

How Is the Trial Designed?

Group I: A2B395 Experimental Treatment 2 Interventions

Participants receive preconditioning lymphodepletion (PCLD) regimen followed by a single dose of A2B395 intravenously on day 0

Who Is Running the Clinical Trial?

A2 Biotherapeutics Inc.

Lead Sponsor

Trials

5

Recruited

1,200+

Published Research Related to This Trial

The study developed a fourth-generation CAR T cell therapy targeting the MUC1 antigen, which is highly expressed in cholangiocarcinoma (CCA) and linked to poor patient outcomes, showing promise as a new treatment option.

Anti-MUC1-CAR4 T cells demonstrated significant cytotoxic activity against CCA cell lines, achieving up to 66% cell killing, while sparing normal cholangiocytes, indicating a targeted and potentially safer therapeutic approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-mucin 1 chimeric antigen receptor T cells for adoptive T cell therapy of cholangiocarcinoma. Supimon, K., Sangsuwannukul, T., Sujjitjoon, J., et al.[2021]

CD19+ CAR T-cells have shown high effectiveness against various cancers, but their complete risk profile, including complications, was not fully understood during initial clinical trials.

Emerging evidence from post-approval studies reveals significant complications associated with CD19+ CAR T-cell therapy, such as cytokine release syndrome and neurotoxicity, indicating that these therapies can affect multiple organ systems and may lead to long-term health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications after CD19+ CAR T-Cell Therapy. Penack, O., Koenecke, C.[2020]

In a pilot clinical trial involving 11 participants with advanced colorectal cancer, vaccination with CEA and Her2 peptides was found to be well tolerated, with 82% of adverse events being mild (Grade 1-2), primarily fatigue and injection site reactions.

The vaccination induced immune responses in 70% of participants and resulted in a median overall survival of 16 months, suggesting potential benefits that warrant further investigation, especially in combination with existing checkpoint-blockade therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot trial of vaccination with Carcinoembryonic antigen and Her2/neu peptides in advanced colorectal cancer. Lynch, KT., Squeo, GC., Kane, WJ., et al.[2021]

Immunotherapy shows promise in treating colorectal cancer, with agents like the monoclonal antibody 17-1A and anti-EGFR antibodies demonstrating the immune system's ability to target and destroy cancer cells.

Clinical trials are currently evaluating various immunotherapeutic strategies, including dendritic cell vaccines and anti-idiotypic antibodies, with some showing potential to enhance anti-tumor responses, although challenges remain due to tumor evasion mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current concepts in immunotherapy for the treatment of colorectal cancer. Indar, A., Maxwell-Armstrong, CA., Durrant, LG., et al.[2019]

Genetically engineered T lymphocytes targeting carcinoembryonic antigen (CEA) led to significant reductions in serum CEA levels (74-99%) in three patients with metastatic colorectal cancer, with one patient showing a notable regression of cancer in the lungs and liver.

All patients experienced severe transient inflammatory colitis as a dose-limiting toxicity, highlighting both the potential efficacy and the risks associated with using CEA as a target in cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis. Parkhurst, MR., Yang, JC., Langan, RC., et al.[2023]

In a study of 108 patients with advanced colorectal cancer and high MSI expression, the combination of PD-1 customization and autoimmune T-cell therapy resulted in a treatment efficiency of 90.74%, significantly higher than the 61.11% efficiency observed in the control group.

The study also found that after treatment, the levels of immune markers like CD107a, perforin, and GranB cells increased in both groups, but the study group showed a more pronounced expression of PD-1, particularly in patients with more advanced cancer stages (grade III-IV).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study of PD-1 Customization and Autoimmune T Cells for Advanced Colorectal Cancer with High MSI Expression. Li, N., Zhang, X., Zhang, Y., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06682793

NCT06682793 | A Study to Evaluate the Safety and ... The goal of this study is to test A2B395, an allogeneic logic-gated Tmod™ CAR T-cell product in subjects with solid tumors including colorectal cancer (CRC) ...

2. a2bio.com a2bio.com/a2-biotherapeutics-presents-initial-safety-and-efficacy-data-from-ongoing-phase-1-2-everest-2-study-including-first-report-of-a-complete-response-to-car-t-cell-therapy-in-a-patient-with-nsclc/

A2 Bio Announces First Patient Dosed in Phase 1/2 ... A2 Biotherapeutics Presents Initial Safety and Efficacy Data from Ongoing Phase 1/2 EVEREST-2 Study, Including First Report of a Complete ...

3. clinicaltrial.be clinicaltrial.be/en/details/458532?per_page=100&only_recruiting=0&only_eligible=0&only_active=0

A Study to Evaluate the Safety and Efficacy of A2B395, an... The purpose of Phase 2 of this study is to determine the further safety and efficacy (how well it treats the solid tumor disease) of A2B395. The ...

4. withpower.com withpower.com/trial/phase-2-neoplasms-squamous-cell-2-2025-d6937

A2B395 CAR T-Cell Therapy for Colorectal Cancer Research shows that T cells engineered to target specific cancer markers can lead to significant reductions in cancer markers and even regression of tumors in ...

5. uclahealth.org uclahealth.org/clinical-trials/study-evaluate-safety-and-efficacy-a2b395-allogeneic-logic

A Study to Evaluate the Safety and Efficacy of A2B395 ... The goal of this study is to test A2B395, an allogeneic logic-gated Tmod™ CAR T-cell product in subjects with solid tumors including colorectal cancer (CRC) ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-01614

A Study to Evaluate the Safety and Efficacy of A2B395 ... The goal of this study is to test A2B395, an allogeneic logic-gated Tmod™ CAR T-cell product in subjects with solid tumors including colorectal cancer (CRC) ...

7. a2bio.com a2bio.com/a2-bio-to-present-early-safety-and-efficacy-data-from-everest-2-study-during-2025-annual-meeting-of-the-society-for-immunotherapy-of-cancer/

A2 Bio Announces First Patient Dosed in Phase 1/2 ... DENALI-1 (NCT06682793) is a seamless Phase 1/2, open-label, nonrandomized study evaluating the safety and efficacy of A2B395, an allogeneic ...