TAC T-cells for the Treatment of HER2-positive Solid Tumors

NCT04727151 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: TAC01-HER2-03KEYNOTE-E77
• Study Type: interventional
• Target: 28
• Locations: 2 countries
• Sites: 11

Brief Summary

TAC01-HER2 is a novel cell therapy that consists of genetically engineered autologous T cells expressing T-cell Antigen Coupler (TAC) that recognizes human epidermal growth factor receptor 2 (HER2). TAC directs T-cells to the targeted antigen (HER2), and once engaged with the target, activates them via the endogenous T cell receptor. This is an open-label, multicenter Phase 1/2 study that aims to establish safety, maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D), pharmacokinetic profile and efficacy of TAC01-HER2 as a monotherapy, and in combination with pembrolizumab, in subjects with HER2 positive gastric and gastroesophageal adenocarcinoma.

Conditions

HER2 Positive Gastric Cancer; Metastatic HER2 Positive Gastroesophageal Junction Cancer

Keywords

HER2 Positive Gastric Cancer; HER2 Positive gastroesophageal adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Phase 1: Incidence of Dose Limiting Toxicities (DLTs)

  A DLT is defined as: * Grade 4 or 5 events determined by the Investigator to be related to the investigational product, with the exception of Grade 4 laboratory abnormalities that are rapidly reversible or correctable without substantial safety concerns. * Grade ≥3 TAC T cell-associated acute infusion reactions persisting for ≥24 hours * Grade ≥3 TAC T cell-associated CRS or neurotoxicity persisting for ≥72 hours * Grade ≥3 cardiovascular or pulmonary toxicity persisting for ≥72 hours * Grade ≥3 immune-related toxicities * Grade ≥3 organ toxicities or non-hematologic toxicities that do not improve to baseline within 7 days * Clinically consequential Grade ≥3 neutropenia or thrombocytopenia lasting ≥30 days from TAC01-HER2 administration. Clinically consequential is defined as febrile neutropenia, serious infection, or bleeding events.

  28 days

Secondary Outcomes (8)

• Phase 1: Determine Recommended Phase 2 Dose (RP2D) for TAC01-HER2 Monotherapy

  Up to 28 Days Post TAC01-HER2 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)

  6 months

• Phase 1: Evaluate Disease Control Rate (DCR)

  24 months

Study Arms (2)

TAC01-HER2

EXPERIMENTAL

Lymphodepletion followed by TAC01-HER2 as a single IV infusion, with a potential for a second dose administration.

Biological: TAC01-HER2

TAC01-HER2 plus pembrolizumab

EXPERIMENTAL

Lymphodepletion followed by TAC01-HER2 as a single IV infusion, followed by pembrolizumab administration.

Biological: TAC01-HER2 plus pembrolizumab

Interventions

TAC01-HER2 BIOLOGICAL

TAC01-HER2 and: * fludarabine and cyclophosphamide, or * clofarabine and cyclophosphamide, or * bendamustine, or * cyclophosphamide

TAC01-HER2

TAC01-HER2 plus pembrolizumab BIOLOGICAL

TAC01-HER2 plus pembrolizumab and: * fludarabine and cyclophosphamide, or * clofarabine and cyclophosphamide, or * bendamustine, or * cyclophosphamide

Also known as: Keytruda

TAC01-HER2 plus pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Written informed consent.
• Age ≥ 18 years at the time of informed consent.
• For Phase 1 and Phase 2:
• Phase 1 monotherapy (completed): HER2 1+, 2+, 3+ by IHC by central laboratory confirmation
• Phase 1 combination therapy and Phase 2: HER2 2+, 3+ by IHC and FISH by central laboratory confirmation
• Histologically confirmed advanced, metastatic, unresectable solid tumors (regardless of PD-L1 expression levels; Phase 1 monotherapy) and histologically confirmed advanced, metastatic, unresectable gastric or esophageal adenocarcinoma (regardless of PD-L1 expression levels for Phase 1 combination therapy and Phase 2) after at least 2 prior lines of therapy (Phase 1) or after at least 2 and no more than 4 prior lines of therapy (Phase 2).
• HER2+ incurable malignancies for which no standard-of-care HER2 targeted therapy exists may be enrolled regardless of the number of prior treatment lines, as long as in the opinion of the investigator the subject would be unlikely to tolerate or derive clinically meaningful benefit from other available treatment options.
• For breast cancer subjects, both prior lines of therapy must have included HER2-targeted agents per current standard-of-care.
• Subjects with solid tumors with genetic alterations and mutations (such as 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.
• ECOG performance status of 0 or 1 at Screening.
• Life expectancy of at least 12 weeks.
• Adequate organ and bone marrow reserve function.
• Recovery to Grade ≤1 or Baseline for any toxicities due to previous therapy.
• Adequate vascular access for leukapheresis.

You may not qualify if:

• Intolerant to any component of TAC01-HER2.
• Prior treatment with any of the following:
• Adoptive cell transfer of any kind, including CAR T cells
• Gene therapy
• Investigational medicinal product within 5 half-lives or 21 days prior to leukapheresis, whichever is shorter.
• Receipt of a live or live-attenuated vaccine within 30 days prior to study treatment.
• Monoclonal antibody (mAb), including PD-1 and PD-L1, therapies within 21 days prior to leukapheresis.
• Radiation within 28 days prior to enrollment. Palliative radiation is allowed up to 14 days prior to enrollment if 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.
• 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 enrollment.
• 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. (Brain metastasis - non-progressive or previously treated and currently stable - are permitted.)
• Active inflammatory neurological disorders (e.g., Guillain-Barre Syndrome, amyotrophic lateral sclerosis, multiple sclerosis).
• Active autoimmune disease (e.g., lupus, rheumatoid arthritis, Sjogren's syndrome) requiring systemic disease modifying agents in the past 2 years.
• Active or uncontrolled hepatitis B or C (HCV ribonucleic acid \[RNA\] positive) infection or any history of or active human immunodeficiency virus (HIV) infection.

Sponsors & Collaborators

• Triumvira Immunologics, Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (11)

Lurie Cancer Center - Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Rutgers Cancer Institute of New Jersey

Newark, New Jersey, 08901, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14203, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Cincinnati Cancer Center

Cincinnati, Ohio, 45267, United States

Location

Sidney Kimmel Cancer Center - Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2C1, Canada

Location

Centre Hospitalier de l'Université de Montréal/Montreal Hospital University Center (CHUM)

Montreal, Quebec, H2X 0A9, Canada

Location

MeSH Terms

Interventions

pembrolizumab

Results Point of Contact

• Title: Maria Apostolopoulou, Clinical Scientist
• Organization: Triumvira Immunologics

mapostolopoulou@triumvira.com

518-892-8426

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Model Details: In Phase 1, escalating doses of TAC01-HER2 will be evaluated to identify the RP2D of the monotherapy arm and the combination arm using the classic keyboard design. In Phase 2, dose expansion groups will further evaluate the safety, efficacy, and PK of the MTD or RP2D for TAC01-HER2 as a monotherapy and in combination with pembrolizumab in subjects with gastric and gastroesophageal adenocarcinoma.

Study Record Dates

• First Submitted: January 20, 2021
• First Posted: January 27, 2021
• Study Start: April 19, 2021
• Primary Completion: December 17, 2023
• Study Completion: March 25, 2024
• Last Updated: June 8, 2025
• Results First Posted: June 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2); US (9)