TAC T-cells for the Treatment of Claudin 18.2 Positive Solid Tumors (TACTIC-3)

NCT05862324 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: TAC01-CLDN18.2-04
• Study Type: interventional
• Target: 113
• Locations: 2 countries
• Sites: 9

Brief Summary

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.

Conditions

Metastatic Solid Tumor

Keywords

Claudin 18.2, Claudin+, Claudin Positive

Outcome Measures

Primary Outcomes (6)

• Phase 1: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)

  Document incidence of DLTs; Type, frequency, and severity of AEs (including clinically significant laboratory abnormalities).

  24 Months

• Phase 2: Evaluate Overall Response Rate (ORR)

  Defined as the percentage of treated subjects with a complete or partial response (CR or PR) as assessed by imaging using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

  24 Months

• Phase 2: Evaluate Duration of Response (DoR)

  Defined as time from first response to disease progression, end of study, start of another anticancer therapy, or death.

  24 Months

• Phase 2: Evaluate Overall survival (OS)

  Defined as time from infusion to death from any cause.

  24 Months

• Phase 2: Evaluate Disease control rate (DCR)

  Defined as the percentage of treated subjects with stable disease (SD), PR, and CR as assessed by imaging using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.

  24 Months

• Phase 2: Evaluate Progression-Free survival (PFS) or Time to progression (TTP)

  Defined as time from infusion to disease progression or death from any cause.

  24 Months

Secondary Outcomes (7)

• Phase 1: Determine MTD or RP2D for TAC01-CLDN 18.2

  Up to 29 Days Post TAC01-CLDN18.2 infusion

• Phase 1: Evaluate Overall Response Rate (ORR)

  24 months

• Phase 1: Evaluate Duration of Response (DoR)

  24 Months

• Phase 1: Evaluate Overall survival (OS)

  24 Months

• Phase 1: Evaluate Disease control rate (DCR)

  24 Months

Other Outcomes (7)

• Phase 1 and Phase 2: Cmax of TAC01-CLDN18.2 (pharmacokinetics; PK).

  24 Months

• Phase 1 and Phase 2: Tmax of TAC01-CLDN18.2 (PK)

  24 Months

• Phase 1 and Phase 2: area under the concentration time curve (AUC) of TAC01-CLDN18.2 (PK)

  24 Months

Study Arms (1)

TAC01-CLDN18.2

EXPERIMENTAL

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

Biological: TAC01-CLDN18.2

Interventions

TAC01-CLDN18.2 BIOLOGICAL

TAC01-CLDN18.2 preceded by lymphodepletion with fludarabine or clofarabine, cyclophosphamide, and nab-paclitaxel.

TAC01-CLDN18.2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed, written informed consent obtained before any study procedures are conducted.
• Age ≥ 18 years at the time of informed consent.
• Tumor tissue samples positive for CLDN18.2 as assessed by central laboratory.
• Histologically confirmed advanced, metastatic, unresectable CLDN18.2+ solid tumors after at least 2 lines of prior therapy (Phase 1) and after at least 2 and no more than 4 prior lines of therapy (Phase 2). Subjects with PDAC may have been treated with 1 line of prior therapy.
• Subjects with incurable Claudin 18.2 expressing malignancies for which no standard-of-care targeted therapy exists may be enrolled regardless of the number of prior treatment lines.
• Specific Phase 1 tumor types include gastric, GEJ, esophageal adenocarcinoma, PDAC, colorectal cancer, cholangiocarcinoma, ovarian mucinous cancer, gallbladder cancer and NSCLC.
• Specific Phase 2 tumor types include gastric and esophageal adenocarcinoma (Group A), PDAC (Group B), and ovarian or NSCLC (Group C). Other tumor types are not eligible.
• Subjects with solid tumors with genetic alterations and mutations (e.g., BRAF, BRCA, EGFR mutations, and ALK translocation) where approved targeted therapies were available to their specific cancers must have been previously treated with such approved therapies, or refused such approved targeted therapy for their cancers, prior to enrollment, or in the opinion of the Investigator would be unlikely to tolerate or derive clinically meaningful benefit from these standard-of-care therapies.
• Measurable disease per RECIST 1.1 at time of enrollment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at Screening.
• Life expectancy of at least 12 weeks.
• Adequate organ and bone marrow reserve function prior to leukapheresis as outlined in protocol.
• Recovery to Grade ≤ 1 or baseline for any toxicities due to previous therapy, except alopecia, anemia, thrombocytopenia, neutropenia, and neuropathy.
• If a subject received major surgery, they must have recovered from the procedure and/or any complications from the procedure prior to starting TAC01-CLDN18.2 therapy.
• Adequate vascular access for leukapheresis as per institutional standards

You may not qualify if:

• Intolerant to any component of TAC01-CLDN18.2
• Prior treatment with any of the following:
• Adoptive cell transfer of any kind, including CAR T cells.
• Gene therapy
• Prior treatment with a CLDN18.2 targeted agent (Phase 2 only)
• Investigational medicinal product within 5 half-lives or 21 days prior to leukapheresis, whichever is shorter.
• Participation in or has participated in a study using an investigational device within 4 weeks prior to the first dose of study treatment.
• Receipt of a live or live-attenuated vaccine within 30 days prior to the first dose of study Intervention. Administration of killed vaccines are allowed.
• Radiation within 28 days prior to leukapheresis. Palliative radiation is allowed up to 14 days prior to leukapheresis if additional non-irradiated lesions are present.
• Chemotherapy or targeted small molecule therapy within 14 days prior to leukapheresis, or within 7 days prior to leukapheresis for erlotinib, gefitinib, afatinib, or crizotinib in NSCLC subjects.
• Colony stimulating factors, including granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin, and other hematopoietic cytokines, within 14 days prior to leukapheresis.
• Immunosuppressive medication within 14 days or corticosteroid treatment \< 72 hours prior to leukapheresis, except for physiological replacement doses (\< 12 mg/m2/24 hours of hydrocortisone or equivalent) and topical or inhaled steroids.
• History or presence of clinically relevant central nervous system (CNS) pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
• Known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study Screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Active inflammatory neurological disorders (e.g., Guillain-Barre Syndrome, amyotrophic lateral sclerosis, multiple sclerosis).

Sponsors & Collaborators

• Triumvira Immunologics, Inc.: lead

Study Sites (9)

University of Southern California

Los Angeles, California, 90033, United States

Location

University of California San Diego

San Diego, California, 92037, United States

Location

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Cincinnati Cancer Center

Cincinnati, Ohio, 45267, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Princess Margaret Cancer Center

Toronto, Ontario, M5G 2C1, Canada

Location

Centre hospitalier de l'Université de Montréal

Montreal, Quebec, H2X 0C1, Canada

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: In Phase 1, escalating doses of TAC01-CLDN18.2 will be evaluated to identify the RP2D using the classic 3+3 dose escalation study design. In Phase 2, dose expansion groups will further evaluate the safety, efficacy, and PK of the MTD or RP2D for TAC01-CLDN18.2 in subjects with gastric and esophageal AC (Group A), PDAC (Group B), and ovarian and NSCLC cancers (Group C). In Phase 2, definitions of eligible CLDN18.2+ IHC expression levels will be based on retrospective analysis of data from Phase 1 in association with clinical efficacy because there are no formal CAP/ASCO definitions for CLDN18.2+ IHC expression levels. In Phase 2, a Simon 2-stage design will be used to enroll up to 57 subjects in Group A and 22 subjects in Group C. Group B will enroll up to 10 subjects without a Simon 2-stage design due to its historically low ORRs. The 10 treated subjects in Group B are designed to seek evidence of potential efficacy in this difficult to treat CLDN18.2+ subpopulation of PDAC.

Study Record Dates

• First Submitted: May 8, 2023
• First Posted: May 17, 2023
• Study Start: August 23, 2023
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: February 14, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (7); CA (2)