TAC01-CLDN18.2 Engineered T-cells for Cancer

(TACTIC-3 Trial)

Not currently recruiting at 9 trial locations

Overseen By Kara M Moss

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Triumvira Immunologics, Inc.

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: CNS pathology, Active autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 29 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new cell therapy designed to help the body's immune cells target and fight certain cancers by focusing on proteins called Claudin 18.2. It primarily examines the safety and effectiveness of this therapy for individuals with advanced or hard-to-treat solid tumors. Participants should have solid tumors that test positive for Claudin 18.2, with no standard treatments available, and must have already tried at least two different therapies. 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 innovative therapy.

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

The trial protocol does not specify if you must stop taking your current medications. However, you must not have had chemotherapy, targeted small molecule therapy, or certain other treatments within specific timeframes before starting the trial. Please consult with the trial team for guidance on your specific medications.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, certain treatments like chemotherapy, targeted therapies, and immunosuppressive medications must be stopped a specific number of days before starting the trial. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that TAC01-CLDN18.2 is likely to be safe for humans?

Research shows that TAC01-CLDN18.2, a type of cell therapy, is under study to assess its safety for people. In earlier studies, patients received this treatment to observe their body's reactions. The results suggest that the therapy is generally well-tolerated, although some patients experienced side effects. These side effects are usually mild, but it's important to know they can occur.

The treatment uses a patient's own T cells (a type of immune cell) modified to specifically attack cancer cells. This targeting might activate the immune system, which can lead to some side effects. Current studies aim to find the best dose that patients can handle without serious reactions.

Since this treatment is in early clinical trials, the main focus is on understanding its safety for humans. The results so far are promising, but ongoing research will provide more information. Those considering joining a trial should discuss the possible risks and benefits with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about TAC01-CLDN18.2 because it represents a novel approach in cancer treatment. Unlike most current cancer therapies that rely on surgery, chemotherapy, or radiation, TAC01-CLDN18.2 uses engineered T-cells to target cancer specifically. These T-cells are designed to home in on a particular protein found on cancer cells, known as CLDN18.2, allowing for more precise attack while sparing healthy cells. This targeted mechanism has the potential to minimize side effects and improve effectiveness, making it a promising option for patients.

What evidence suggests that TAC01-CLDN18.2 might be an effective treatment for cancer?

Research has shown that TAC01-CLDN18.2 holds promise for treating cancer. An earlier study found that lower doses of TAC01-CLDN18.2 were safe and effective in patients who had undergone many previous treatments. This treatment uses specially designed T-cells to target a protein called Claudin 18.2, present in some cancer cells. Early lab results indicate these T-cells can generate a strong and lasting response against tumors with this protein. This suggests TAC01-CLDN18.2 could effectively treat cancers with Claudin 18.2. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced solid tumors that test positive for Claudin 18.2 and have undergone at least two prior therapies (one for pancreatic cancer). Participants must be in good health otherwise, not pregnant, willing to use contraception, and without a history of severe allergies or reactions to similar treatments.

Inclusion Criteria

Subjects with hepatitis B surface antigen (HBsAg) positive must meet specified criteria

My cancer is advanced, cannot be surgically removed, and tests positive for CLDN18.2.

Life expectancy of at least 12 weeks

Exclusion Criteria

History of drug-induced pneumonitis/interstitial lung disease

I recently had radiation, chemotherapy, or targeted therapy.

I have a history of certain brain or nervous system conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lymphodepletion followed by a single IV infusion of TAC01-CLDN18.2

Up to 29 days

Follow-up

Participants are monitored for safety, efficacy, and pharmacokinetics, including disease control rate and overall survival

24 months

Open-label extension (optional)

Participants may continue to receive TAC01-CLDN18.2 if they benefit from the treatment

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• TAC01-CLDN18.2

Trial Overview TAC01-CLDN18.2 cell therapy is being tested on patients with specific types of solid tumors. This therapy involves genetically modified T cells targeting the Claudin 18.2 protein on tumor cells. The study aims to find the safest dose and see how well it works.

How Is the Trial Designed?

Group I: TAC01-CLDN18.2 Experimental Treatment 1 Intervention

Lymphodepletion followed by TAC01-CLDN18.2 as a single IV infusion.

Who Is Running the Clinical Trial?

Triumvira Immunologics, Inc.

Lead Sponsor

Trials

3

Recruited

140+

Published Research Related to This Trial

In a phase 1 clinical trial involving 37 patients with CLDN18.2-positive digestive system cancers, CT041 CAR T cell therapy demonstrated a promising overall response rate of 48.6% and a disease control rate of 73.0%.

The treatment showed an acceptable safety profile, with all patients experiencing grade 3 or higher hematologic toxicity but no severe cytokine release syndrome or neurotoxicities, indicating that CT041 could be a viable option for patients with previously treated gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results. Qi, C., Gong, J., Li, J., et al.[2022]

The study identified claudin 6 (CLDN6) as a promising target for adoptive cell therapy (ACT) in ovarian cancer, as it is frequently expressed on cancer cells but not on healthy immune cells, suggesting a potential for selective targeting.

Specific T-cell receptors (TCRs) that recognize CLDN6 were isolated from ovarian cancer patients, and engineered T cells demonstrated the ability to effectively kill cancer cells expressing CLDN6, indicating the therapeutic potential of these TCRs for treating ovarian and other solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of Claudin 6-specific HLA class I- and HLA class II-restricted T cell receptors for cellular immunotherapy in ovarian cancer. Matsuzaki, J., Lele, S., Odunsi, K., et al.[2022]

CLDN18.2-specific CAR T cells demonstrated significant antitumor activity in both cancer cell line xenograft models and patient-derived tumor xenograft (PDX) models, with tumor volumes drastically reduced compared to untransduced T cells (P < .001).

The CAR T cells showed no harmful effects on normal organs, including gastric tissues, indicating a promising safety profile for this treatment strategy in gastric cancer and potentially other CLDN18.2-positive tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Claudin18.2-Specific Chimeric Antigen Receptor Engineered T Cells for the Treatment of Gastric Cancer. Jiang, H., Shi, Z., Wang, P., et al.[2020]

IL-15 modification significantly enhances the expansion, survival, and antitumor activity of CLDN18.2-targeting CAR-T cells in murine models, leading to improved tumor suppression compared to standard CAR-T cells.

In vivo studies showed that IL-15-expressing CAR-T cells not only infiltrated tumors more effectively but also provided a survival advantage in certain tumor models, highlighting their potential for clinical evaluation in patients with CLDN18.2-positive tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL-15 armoring enhances the antitumor efficacy of claudin 18.2-targeting CAR-T cells in syngeneic mouse tumor models. Shi, H., Li, A., Dai, Z., et al.[2023]

CAR T cells engineered to target the tumor-associated glycoprotein-72 (TAG72) and modified with membrane-bound IL-12 (mbIL12) show enhanced anti-tumor activity and improved T cell proliferation, demonstrating significant efficacy in human ovarian cancer models.

The use of mbIL12 in CAR T cells not only promotes effective tumor cell killing but also positively impacts the immunosuppressive tumor microenvironment, suggesting a promising approach for treating both local and systemic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antigen-dependent IL-12 signaling in CAR T cells promotes regional to systemic disease targeting. Lee, EHJ., Murad, JP., Christian, L., et al.[2023]

A phase I trial of CAR T-cell therapy targeting claudin 18.2, which is mainly found in stomach mucosal cells, demonstrated promising efficacy against advanced digestive system cancers.

The therapy showed acceptable safety, indicating it could be a viable treatment option for patients with solid tumors, which have traditionally been challenging to treat with CAR T-cell therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastric Cancer CAR T-cell Target Antigen ID'd. [2022]

The ongoing phase 1/2 trial of CAR T cells targeting the oncofetal antigen Claudin 6 (CLDN6) in patients with relapsed/refractory solid tumors showed manageable toxicity, with 46% of patients experiencing cytokine release syndrome, indicating a generally safe profile for this treatment approach.

Among 21 evaluable patients, the treatment demonstrated an objective response rate of 33%, with a notable 57% response rate in patients with germ cell tumors, suggesting potential efficacy in this specific subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CLDN6-specific CAR-T cells plus amplifying RNA vaccine in relapsed or refractory solid tumors: the phase 1 BNT211-01 trial. Mackensen, A., Haanen, JBAG., Koenecke, C., et al.[2023]

A specific CTL clone was successfully isolated that recognizes the claudin-1 protein in ovarian cancer cells, demonstrating the potential for targeted immunotherapy against this type of cancer.

The study shows that HLA-modified cancer cells can effectively serve as artificial antigen-presenting cells to generate CTLs that are specific to cancer antigens, which could enhance the development of personalized cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An HLA-modified ovarian cancer cell line induced CTL responses specific to an epitope derived from claudin-1 presented by HLA-A*24:02 molecules. Kondo, S., Demachi-Okamura, A., Hirosawa, T., et al.[2013]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.828

A phase 1/2 study evaluating the safety and efficacy of ... Treatment with the lower doses of TAC01-CLDN18.2 is safe and shows promising clinical activity in a heavily pre-treated cancer population.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05862324?term=claudin%2018.2&rank=3

TAC T-cells for the Treatment of Claudin 18.2 Positive Solid ... TAC01- CLDN18.2 is a novel cell therapy that consists of genetically engineered autologous T cells expressing T-cell Antigen Coupler (TAC) that recognizes ...

3. aacrjournals.org aacrjournals.org/cancerimmunolres/article/13/1/35/750785/Preclinical-Development-of-T-Cells-Engineered-to

Preclinical Development of T Cells Engineered to Express a T ... Thus, the data demonstrate that CLDN18.2-TAC T cells can induce a specific and long-lasting antitumor response in various CLDN18.2-positive solid tumor models ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39404622/

Preclinical Development of T Cells Engineered to Express ... The data demonstrate that CLDN18.2-TAC T cells can induce a specific and long-lasting antitumor response in various CLDN18.2-positive solid tumor models.

5. asco.org asco.org/abstracts-presentations/ABSTRACT432764

First-in-human phase 1/2 trial evaluating TAC01-CLDN18. ... A phase 1/2 study evaluating the safety and efficacy of autologous TAC T cells in subjects with claudin 18.2+ advanced solid tumors. First Author: Davendra ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e14519

A phase 1/2 study evaluating the safety and efficacy of ... The purpose of this study is to determine the safety of autologous TAC T cell administration to subjects with claudin 18.2+ advanced solid tumors.