A2B530 CAR T Therapy for Solid Cancers

(EVEREST-1 Trial)

Not currently recruiting at 10 trial locations

Overseen By Wen-Kai Weng, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: A2 Biotherapeutics Inc.

Disqualifiers: Local therapy, Stem cell transplant, Organ transplant, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called A2B530, a type of CAR T-cell therapy, for individuals with certain solid cancers such as colorectal, pancreatic, and lung cancer. The first phase aims to determine the safest dose, while the second phase evaluates its effectiveness in targeting cancer cells without harming healthy ones. It suits those whose tumors express a specific protein (CEA) and who have not succeeded with other treatments. Participants should have tumors that cannot be surgically removed or treated with standard therapies. They must be willing to adhere to the study's schedule, including safety follow-ups. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot have had cancer therapy within 3 weeks or 3 half-lives of the A2B530 infusion. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that A2B530 CAR T therapy is likely to be safe for humans?

Research has shown that A2B530, a new CAR T-cell therapy, could be promising for treating solid tumors, with a focus on safety. Early studies found that this treatment aims to avoid common problems with CAR T therapies, such as mistakenly attacking healthy cells, known as on-target, off-tumor toxicity.

In these studies, researchers tested A2B530 on patients with solid tumors, including colorectal, pancreatic, and lung cancers. The treatment was generally well-tolerated. Some patients experienced side effects, but these are common with many new treatments and are closely monitored by the researchers.

Overall, these early findings suggest that A2B530 is safe for humans, with the goal of finding the best dose that balances effectiveness and safety. However, ongoing studies are essential to fully understand its safety. ^{1 2 3 4 5}

Why are researchers excited about this possible treatment for solid cancers?

Researchers are excited about A2B530 CAR T Therapy because it represents a new way to tackle solid cancers. Unlike traditional treatments like chemotherapy or radiation, A2B530 uses engineered T-cells, which are part of the immune system, to specifically target and attack cancer cells. This method not only aims to enhance precision in targeting tumors but also minimizes damage to healthy cells. The single-dose administration post-preconditioning lymphodepletion suggests a potentially quicker and more focused therapeutic action, which is a promising advancement over existing options.

What evidence suggests that A2B530 might be an effective treatment for solid tumors?

Research has shown that A2B530, a type of CAR T-cell therapy, might effectively target solid tumors such as colorectal, pancreatic, and non-small cell lung cancers. This treatment enables T-cells, part of the immune system, to specifically attack cancer cells while sparing healthy ones. A2B530 also addresses common issues in similar treatments, such as harming healthy tissues. Early studies suggest that patients tolerate the treatment well, with no serious side effects reported. This promising method uses the immune system to fight cancer more safely and effectively. ^{1 2 3 5 6}

Who Is on the Research Team?

Eric Ng, MD

Principal Investigator

A2 Biotherapeutics Inc.

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

I can carry out all my daily activities without help.

You are expected to live for at least 3 more months.

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

Exclusion Criteria

I haven't had a new blood clot in my lungs or legs in the last 3 months.

I am not pregnant or breastfeeding.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preconditioning Lymphodepletion (PCLD) Regimen

Participants receive a preconditioning lymphodepletion regimen before the infusion of A2B530 Tmod CAR T cells

1 week

Treatment

Participants receive a single dose of A2B530 intravenously on day 0

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events and dose limiting toxicities

24 months

What Are the Treatments Tested in This Trial?

Interventions

• A2B530

Trial Overview

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.

How Is the Trial Designed?

Group I: A2530 Experimental Treatment 2 Interventions

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

A2B530 is already approved in United States for the following indications:

Approved in United States as A2B530 for:

• Colorectal cancer with germline heterozygous HLA-A*02-positive disease expressing carcinoembryonic antigen and lost HLA-A*02 expression

Who Is Running the Clinical Trial?

A2 Biotherapeutics Inc.

Lead Sponsor

Trials

5

Recruited

1,200+

Tempus AI

Industry Sponsor

Trials

18

Recruited

20,700+

Tempus Labs

Industry Sponsor

Trials

17

Recruited

20,200+

Published Research Related to This Trial

CAR T-cell therapies have shown promising and potentially curative effects in treating blood cancers, but their effectiveness as standalone treatments for solid tumors has been limited.

Combining CAR T-cell therapy with other treatments, such as chemotherapy or radiotherapy, may enhance therapeutic efficacy for solid tumors, suggesting that combination strategies could be more effective than monotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapy: A feasibility strategy for CAR-T cell therapy in the treatment of solid tumors. Xu, J., Wang, Y., Shi, J., et al.[2022]

CAR T cell therapy has shown strong effectiveness against leukemia and lymphoma, but faces challenges in treating solid tumors due to issues like T cell persistence and the tumor microenvironment.

Current research is focused on improving CAR T cell design and strategies to enhance T cell longevity and overcome tumor heterogeneity, with the goal of making this therapy effective for solid cancers, although it remains unproven at this stage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategies for Improving the Efficacy of CAR T Cells in Solid Cancers. Kyte, JA.[2022]

The study demonstrated that an optimized single-chain T cell receptor (scTCR) targeting the p53 tumor antigen can effectively eradicate tumors without causing harmful autoimmunity, indicating a high safety profile for this TCR gene therapy.

Adoptive T cell transfer (ACT) using the scTCR led to complete tumor protection and the development of a long-lasting, antigen-specific memory T cell response in mouse models, showcasing its therapeutic efficacy against p53-associated cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Potent Tumor-Reactive p53-Specific Single-Chain TCR without On- or Off-Target Autoimmunity In Vivo. Echchannaoui, H., Petschenka, J., Ferreira, EA., et al.[2020]

CAR-T cell therapy shows promising efficacy in treating solid tumors, with a 100% clinical benefit in epithelial ovarian cancer and varying success rates in other cancers, such as 70-82% in gastrointestinal tumors and 63% in small-cell lung cancer, based on a review of 29 studies involving 265 patients.

The therapy appears to be safe, as no serious CAR-T cell specific toxicities were reported in the studies reviewed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy for Solid Tumors: Are we Still That Far? a Systematic Review of Literature. Karam, A., Mjaess, G., Martinez Chanza, N., et al.[2022]

CD22-targeting CAR T-cell therapies show high complete response rates, with 68% in acute lymphoblastic leukemia (ALL) and 64% in non-Hodgkin's lymphoma (NHL), indicating their efficacy in treating these malignancies.

The incidence of severe side effects, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), is low, suggesting that these therapies are relatively safe, especially with dual-targeting CAR T-cells not increasing toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of CD22 CAR T-cells alone or in combination with CD19 CAR T-cells. Fergusson, NJ., Adeel, K., Kekre, N., et al.[2023]

In a study of 170 patients with refractory/relapsed diffuse large B-cell lymphoma (DLBCL), TP53 mutations were found to be a poor prognostic factor for overall survival in patients receiving conventional therapies, with a median survival of 12 months for those with mutations compared to not reached for those without.

However, in patients treated with CAR T-cell therapy, TP53 mutation status did not significantly impact overall survival, suggesting that CAR T-cell therapy may overcome the negative effects of TP53 mutations seen in conventional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of TP53 Mutation on Survival of Diffuse Large B-Cell Lymphoma in the CAR T-Cell Era. Porpaczy, E., Wohlfarth, P., Königsbrügge, O., et al.[2021]

CAR-T therapy has shown great promise in treating blood cancers by using modified T cells to target specific tumor antigens, but its effectiveness against solid tumors is still limited due to challenges like the tumor microenvironment and lack of specific targets.

Recent advancements, including CRISPR-based modifications and the use of progenitor-like T cells, are being explored to enhance CAR-T therapy's application in solid tumors, with several studies expected to enter clinical trials soon.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cells applied to solid tumors. Zhou, Z., Tao, C., Li, J., et al.[2022]

CAR T-cell therapy has shown remarkable success in treating blood cancers, with two therapies, Kymriah and Yescarta, receiving FDA and EMA approval.

However, applying CAR T-cell therapy to solid tumors faces significant challenges, such as the diverse nature of tumor antigens and the suppressive environment around tumors, which hinder T-cell effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Clinical Evidence and Potential Solutions to Increase Benefit of CAR T-Cell Therapy for Patients with Solid Tumors. Alcantara, M., Du Rusquec, P., Romano, E.[2021]

Engineered T-cell receptor (TCR) and CAR T therapies have shown promising clinical responses in select solid tumors, building on the success seen in hematological malignancies with CAR T treatments.

Recent advancements in target selection, T-cell activation, and overcoming the immunosuppressive tumor environment are expected to enhance the efficacy of these therapies in solid tumors, although healthcare facilities will need to adapt to implement these treatments effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cell receptor and chimeric antigen receptor in solid cancers: current landscape, preclinical data and insight into future developments. Azizi, AA., Pillai, M., Thistlethwaite, FC.[2020]

Chimeric antigen receptor (CAR) T-cell therapies have shown great success in treating hematological cancers, but their effectiveness against solid tumors is limited due to the challenging tumor microenvironment.

To improve CAR T-cell efficacy in solid tumors, future strategies may involve combination therapies that target both the tumor and its immunosuppressive mechanisms, as well as next-generation CAR designs that enhance targeting precision and resistance to T-cell exhaustion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approaches for refining and furthering the development of CAR-based T cell therapies for solid malignancies. Hull, CM., Maher, J.[2022]

A study involving 163 patients with metastatic solid cancers identified 78 with TP53 mutations, leading to the development of a library of 39 T-cell receptors (TCRs) that target these shared mutations, which could potentially broaden the use of adoptive cellular therapy (ACT) in cancer treatment.

While initial treatments using tumor-infiltrating lymphocytes (TILs) showed limited clinical responses, one patient treated with engineered T cells targeting a specific TP53 mutation experienced a significant tumor regression, suggesting that TCRs targeting shared neoantigens may be a promising avenue for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive Cellular Therapy with Autologous Tumor-Infiltrating Lymphocytes and T-cell Receptor-Engineered T Cells Targeting Common p53 Neoantigens in Human Solid Tumors. Kim, SP., Vale, NR., Zacharakis, N., et al.[2022]

CAR T-cell immunotherapy, which involves genetically modifying T cells to target cancer cells, has shown promising results, especially in treating B-cell malignancies with several patients achieving complete and durable responses.

Current research is expanding CAR T-cell therapy to solid tumors, specifically targeting members of the ErbB family, indicating a potential for broader applications in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ErbB-targeted CAR T-cell immunotherapy of cancer. Whilding, LM., Maher, J.[2022]

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