Triumvira Immunologics’ TAC T-cell Therapy TAC01-CLDN18.2 to be Evaluated in Phase 1/2 Clinical Trail for Solid Tumors

Triumvira Immunologics’ TAC01-CLDN18.2, an investigational autologous T-cell antigen coupler (TAC) CLDN18.2-targeted T-cell product, is set to be evaluated in the first-in-human phase 1/2 TACTIC-3 (NCT05862324) clinical trial for patients with various types of solid tumors.^1,2 Triumvira recently presented a poster detailing the design of the dose escalation and dose expansion clinical trial at the 2024 American Society of Clinical Oncology (ASCO) Genitourinary Cancers (GI) Symposium, held January 18-20, in San Francisco, California.

TAC01-CLDN18.2 integrates TAC, Triumvira’s proprietary chimeric receptor that is intended to activate and direct T-cells against tumor cells. TAC01-CLDN18.2 specifically expresses the CLDN18.2 TAC with the intention of targeting tumor cells that are CLDN18.2-positive. The TACTIC-3 trial is currently recruiting patients with gastric cancer, gastroesophageal cancer (GEJ), esophageal adenocarcinoma (AC), non–small cell lung cancer (NSCLC), cholangiocarcinoma, pancreatic ductal AC (PDAC), ovarian mucinous cancer, and colorectal cancer.

The phase 1 dose escalation portion of the study will follow a standard 3+3 design and aims to treat 9 to 24 patients in total. Four different dose levels will be evaluated: 1-3x10⁵ cells/kg, 6-8x10⁵ cells/kg, 1-3x10⁶ cells/kg, and 6-8x10⁶ cells/kg. Patients with gastric cancer, GEJ, esophageal AC, NSCLC, PDAC, cholangiocarcinoma, ovarian mucinous cancer, and colorectal cancer are eligible for this portion of the trial. These participants must have cancer that is negative for expression of HER2 and must have had at least 2 lines of prior therapy.

The phase 2 dose expansion portion will utilize a Simon 2-stage design for cohorts referred to as Groups A and C. Group A will include up to 57 patients with esophageal AC or gastric cancer and Group C will include up to 22 patients with ovarian cancer or NSCLC. A separate cohort referred to as Group B will include up to 10 patients with PDAC and will initially seek to determine the overall response rate (ORR) in these patients. Participants in the phase 2 portion must have had at least 2 prior lines of therapy, but not more than 4 prior lines of therapy. This portion does not require HER2 negativity.

The objective of the phase 1 portion is to determine the maximum tolerated dose and recommended phase 2 dose, along with safety and tolerability, which will be assessed by the incidence of dose-limiting toxicities, adverse events (AEs), and clinically significant lab abnormalities. The objective of the phase 2 portion includes assessing the ORR, duration of response, overall survival, disease control rate, progression-free survival, and time to progression. The phase 2 portion will also assess the type, frequency, and severity of AEs and clinically significant lab abnormalities during a 24-month timeframe. Exploratory outcome measures for TACTIC-3 include an investigation of biomarkers predicting response and an assessment of manufacturing feasibility.

The trial includes patients aged 18 years and older who have measurable disease a measured by RECIST 1.1 at enrollment, an Eastern Cooperative Oncology Group score of 0 or 1, a life expectancy of 12 weeks, adequate organ and bone marrow function before leukapheresis, and adequate vascular access for leukapheresis. Patients who have previously been treated with adoptive cell transfer or gene therapy; patients who have known active central nervous system metastases, carcinomatous meningitis, or inflammatory neurological disorders; and patients who have received a live or live-attenuated vaccine in the 30 days prior to the first dosing with TAC01-CLDN18.2 will be excluded from participation. Additional inclusion and exclusion criteria exist.

Triumvira also presented a separate poster at the conference detailing results from their phase 1/2 TACTIC-2 clinical trial (NCT04727151).³ TACTIC-2 is evaluating TAC01-HER2, an autologous TAC T-cell product that targets HER2, in patients with advanced solid tumors expressing HER2.

"We are delighted to showcase the latest clinical developments of our phase 1/2 study investigating the safety and efficacy of autologous TAC-T cells targeting HER2+ relapsed or refractory solid tumors and our first-in-human phase 1/2 trial targeting CLDN18.2-positive solid tumors," Paul Lammers, MD, MSc, the CEO of Triumvira Immunologics, said in a statement.² "Our abstract presentations at the ASCO Gastrointestinal Cancers Symposium underscores our dedication to pioneering advancements in autologous T-cell therapy and unveils promising clinical data from our ongoing phase 1/2 studies, shedding light on the safety and efficacy of autologous TAC01-HER2 and TAC01-CLDN18.2 in the challenging landscape of solid tumors."

REFERENCES
1. Dumbrava EE, Sohal DP, Olson D, et al. First-in-human phase 1/2 trial evaluating TAC01-CLDN18.2 autologous T cells in CLDN18.2-positive solid tumors. Presented at: 2024 ASCO GI; January 18-20; San Francisco, California. Abstract #TPS419
2. Triumvira Immunologics to present clinical data at the 2024 ASCO gastrointestinal cancers symposium. News release. Triumvira Immunologics. December 19, 2023. Accessed January 19, 2024. https://www.prnewswire.com/news-releases/triumvira-immunologics-to-present-clinical-data-at-the-2024-asco-gastrointestinal-cancers-symposium-302018607.html
3. Schlechter BL, Dumbrava EE, George MA, et al. A phase I/II trial investigating safety and efficacy of autologous TAC01-HER2 in relapsed or refractory solid tumors. Presented at: 2024 ASCO GI; January 18-20; San Francisco, California. Abstract #747