113 Participants Needed

TAC01-CLDN18.2 Engineered T-cells for Cancer

(TACTIC-3 Trial)

Recruiting at 8 trial locations
KM
Overseen ByKara M Moss
Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: Triumvira Immunologics, Inc.
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

TAC01-CLDN18.2 is a novel cell therapy that consists of genetically engineered autologous T cells expressing T-cell Antigen Coupler (TAC) that recognizes Claudin 18.2. TAC directs T-cells to the targeted antigen (CLDN 18.2), and once engaged with the target, activates them via the endogenous T cell receptor. This is an open-label, multicenter Phase ½ study that aims to establish safety, maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D), pharmacokinetic profile and efficacy of TAC01-CLDN18.2.

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.

What data supports the idea that TAC01-CLDN18.2 Engineered T-cells for Cancer is an effective treatment?

The available research shows that TAC01-CLDN18.2 Engineered T-cells, which target the protein Claudin 18.2, have shown promising results in treating certain cancers. In a study involving solid tumors, 33% of patients experienced a reduction in tumor size, and 67% had their disease stabilized. Another study demonstrated that these T-cells, when modified with IL-15, significantly suppressed tumor growth in mice. Additionally, a trial targeting gastric cancer showed promising effectiveness and safety. These findings suggest that TAC01-CLDN18.2 could be a beneficial treatment option for cancers expressing Claudin 18.2.12345

What data supports the effectiveness of the treatment TAC01-CLDN18.2?

Research shows that T-cells engineered to target Claudin 18.2, a protein found in some cancer cells, have shown promising results in treating solid tumors. In studies, these engineered T-cells have demonstrated the ability to recognize and kill cancer cells expressing Claudin 18.2, suggesting potential effectiveness in treating cancers like gastric cancer.12345

What safety data exists for TAC01-CLDN18.2 T-cells for cancer treatment?

The safety data for TAC01-CLDN18.2, also known as CLDN18.2-targeted CAR T cells, indicates that these treatments have shown manageable toxicity profiles in clinical trials. In a phase 1 trial for gastrointestinal cancers, all patients experienced grade 3 or higher hematologic toxicity, and 94.6% had grade 1 or 2 cytokine release syndrome (CRS), but no grade 3 or higher CRS, neurotoxicities, treatment-related deaths, or dose-limiting toxicities were reported. Another study on CLDN6-specific CAR T cells reported manageable toxicity with cytokine release syndrome occurring in 46% of patients, including one grade 3 event. Overall, these treatments have shown promising efficacy with an acceptable safety profile in heavily pretreated patients with CLDN18.2-positive cancers.12367

What safety data exists for TAC01-CLDN18.2 Engineered T-cells for Cancer?

In a study of Claudin18.2-targeted CAR T cells for digestive system cancers, all patients experienced some blood-related side effects, but no severe cytokine release syndrome (a condition where the immune system overreacts) or neurotoxicities were reported. Another study on Claudin 6-targeted CAR T cells showed manageable safety with some patients experiencing cytokine release syndrome, but these effects were generally mild and resolved without long-term issues.12367

Is the treatment TAC01-CLDN18.2 a promising treatment for cancer?

Yes, TAC01-CLDN18.2 is a promising treatment for cancer because it targets a specific protein, Claudin 18.2, which is found in many solid tumors. This targeted approach can help the immune system attack cancer cells more effectively, potentially leading to better outcomes for patients.12389

How is the TAC01-CLDN18.2 treatment different from other cancer treatments?

TAC01-CLDN18.2 is unique because it uses engineered T-cells specifically targeting Claudin 18.2, a protein found in certain cancer cells, to enhance the immune system's ability to attack tumors. This approach is different from traditional treatments as it involves modifying the patient's own T-cells to recognize and destroy cancer cells, offering a personalized and potentially more effective therapy for cancers expressing Claudin 18.2.12389

Eligibility Criteria

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
See 10 more

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.
See 10 more

Timeline

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

Treatment Details

Interventions

  • TAC01-CLDN18.2
Trial OverviewTAC01-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.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: TAC01-CLDN18.2Experimental Treatment1 Intervention
Lymphodepletion followed by TAC01-CLDN18.2 as a single IV infusion.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Triumvira Immunologics, Inc.

Lead Sponsor

Trials
3
Recruited
140+

Findings from Research

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.
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]
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.
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]
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.
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]

References

Identification of Claudin 6-specific HLA class I- and HLA class II-restricted T cell receptors for cellular immunotherapy in ovarian cancer. [2022]
CLDN6-specific CAR-T cells plus amplifying RNA vaccine in relapsed or refractory solid tumors: the phase 1 BNT211-01 trial. [2023]
IL-15 armoring enhances the antitumor efficacy of claudin 18.2-targeting CAR-T cells in syngeneic mouse tumor models. [2023]
Gastric Cancer CAR T-cell Target Antigen ID'd. [2022]
Claudin18.2-Specific Chimeric Antigen Receptor Engineered T Cells for the Treatment of Gastric Cancer. [2020]
Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results. [2022]
Claudin-6 CAR T Cells Are Safe and Have Potential Clinical Activity. [2023]
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. [2013]
Antigen-dependent IL-12 signaling in CAR T cells promotes regional to systemic disease targeting. [2023]