Evaluate TCRT-ESO-A2 Autologous T Cells Expressing TCR Specific for NY-ESO-1 in Subjects With Advanced Solid Tumors

NCT04878484 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: AX TCRT 001
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

TCRT-ESO-A2 is an autologous cell therapy comprised of a subject's T cells stimulated ex vivo and transduced with a lentiviral vector encoding an affinity enhanced TCR targeting tumor-associated antigen NY-ESO-1. This study will investigate the safety, tolerability, activity, and pharmacokinetics/ pharmacodynamics of TCRT-ESO-A2 infusion. A maximum tolerated dose study of TCRT-ESO-A2 in subjects with advanced malignancies expressing NY-ESO-1 is considered to be an acceptable risk. Once safety, tolerability, and pharmacokinetic/pharmacodynamic data are available, the activity of TCRT-ESO-A2 in NY-ESO-1-positive tumors may be explored further.

Conditions

Advanced Solid Tumor

Keywords

NY-ESO-1

Outcome Measures

Primary Outcomes (1)

• Dose Escalation: Evaluate up to Eighteen Subjects With Tumors Expressing TCRT-ESO-A1 and Having Dose Limiting Toxicity Adverse Events as Assessed by CTCAE-Version 5

  TCRT-ESO-A2 maximum tolerated dose as assessed by the occurrence of dose-limiting toxicity adverse events at least possibility related to TCRT-ESO - A2 in two of six subjects who received TCRT-ESO-A2

  Day 28

Secondary Outcomes (30)

• Dose Escalation: Tumor Response for Partial Response as Assessed by RECIST 1.1.

  Day 28 and every 3 months until disease progression averaging one year

• Dose Escalation: Tumor Response Stable Disease as Assessed by RECIST 1.1.

  Day 28 and every 3 months until disease progression averaging one year

• Dose Escalation: Tumor Response Disease Progression as Assessed by RECIST 1.1.

  Day 28 and every 3 months until disease progression averaging one year

• Dose Escalation: Tumor Response Overall Survival as Assessed by RECIST 1.1.

  Day 28 and every 3 months until disease progression averaging one year

• Dose Escalation: Tumor Response Progression-Free Survival as Assessed by RECIST 1.1.

  Day 28 and every 3 months until disease progression averaging one year

Other Outcomes (36)

• Explore Persistence of Genetically Modified T cells in vivo.

  Baseline to disease progression averaging one year

• Explore Phenotype of Genetically Modified T cells in vivo.

  Baseline to disease progression averaging one year

• Explore Presence of CA-125 Tumor Immune Biomarker Before TCRT-ESO-A2 Infusion

  Baseline to disease progression averaging one year

Study Arms (3)

Cohort 1: TCRT-ESO-A2: 0.3 × 1010 TCRT-ESO-A2 cells * ±30%

EXPERIMENTAL

Subjects will be evaluated for DLTs up to 28 days post-TCRT-ESO-A2 infusion. Enrollment into a dose level will be suspended if two of no more than six subjects at a dose level experience dose-limiting toxicity. Prior to increasing the dose, a cohort management meeting will be held after the final enrolled subject has been followed for up to28 days. The decision to increase to the next dose level will be a joint decision of the clinical site Investigators and Sponsor. At each cohort, there will be at least 7 days between infusion of each subject in the cohort.

Biological: TCRT-ESO-A2

Cohort 2: TCRT-ESO-A2: 1.0 × 1010 TCRT-ESO-A2 cells ±30%

EXPERIMENTAL

Subjects will be evaluated for DLTs up to 28 days post-TCRT-ESO-A2 infusion. Enrollment into a dose level will be suspended if two of no more than six subjects at a dose level experience dose-limiting toxicity. Prior to increasing the dose, a cohort management meeting will be held after the final enrolled subject has been followed for up to28 days. The decision to increase to the next dose level will be a joint decision of the clinical site Investigators and Sponsor. At each cohort, there will be at least 7 days between infusion of each subject in the cohort. The decision to increase to the next dose level will be a joint decision of the clinical site Investigators and Sponsor.

Biological: TCRT-ESO-A2

Cohort 3: TCRT-ESO-A2 : 3.0 × 1010 TCRT-ESO-A2 cells ±30%

EXPERIMENTAL

Subjects will be evaluated for DLTs up to 28 days post-TCRT-ESO-A2 infusion. Enrollment into a dose level will be suspended if two of no more than six subjects at a dose level experience dose-limiting toxicity. Prior to increasing the dose, a cohort management meeting will be held after the final enrolled subject has been followed for up to28 days. The decision to increase to the next dose level will be a joint decision of the clinical site Investigators and Sponsor. At each cohort, there will be at least 7 days between infusion of each subject in the cohort.

Biological: TCRT-ESO-A2

Interventions

TCRT-ESO-A2 BIOLOGICAL

TCRT-ESO-A2 is an autologous cell therapy comprised of a subject's T cells stimulated ex vivo and transduced with a lentiviral vector encoding an affinity enhanced TCR targeting tumor-associated antigen NY-ESO-1.

Cohort 1: TCRT-ESO-A2: 0.3 × 1010 TCRT-ESO-A2 cells * ±30%; Cohort 2: TCRT-ESO-A2: 1.0 × 1010 TCRT-ESO-A2 cells ±30%; Cohort 3: TCRT-ESO-A2 : 3.0 × 1010 TCRT-ESO-A2 cells ±30%

Eligibility Criteria

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

You may qualify if:

• Able to understand and voluntarily sign an informed consent form (ICF).
• Age ≥18 years of age at the time of informed consent.
• HLA-A\*0201 positive by high resolution testing.
• Any of the following solid tumors with positive NY-ESO-1 expression characterized by IHC:
• Head and neck cancer with ≥85% of tumor cells scored ≥1+.
• Hepatocellular carcinoma with ≥20% of tumor cells scored ≥1+.
• Lung squamous cell carcinoma with ≥20% of tumor cells scored ≥1+.
• Synovial sarcoma with ≥65% of cells scored ≥1+.
• Triple-negative breast cancer with ≥20% of cells scored ≥1+.
• Received standard curative or palliative therapy including any targeted therapy based on mutation status for their cancer, or advanced solid tumors for which there is no accepted therapy, standard therapies are no longer effective, or the subject refuses additional standard therapy.
• Measurable disease as defined per RECIST 1.1 (Eisenhauer 2009).
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1.
• Life expectancy of \>4 months.
• Adequate hematologic status as demonstrated by not requiring transfusion support or granulocyte-colony stimulating factor (G-CSF) to maintain:
• White blood cell count ≥3,000/mcL.

You may not qualify if:

• Eligible subjects must not have/be:
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease or AIDS).
• Known allergic reactions to any component of the treatments in this study.
• Echocardiography (ECHO) or multigated acquisition scan (MUGA) indicative of left ventricular ejection fraction (LVEF) ≤45%.
• Eligible subjects must not have/be:
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease or AIDS).
• Known allergic reactions to any component of the treatments in this study.
• Echocardiography (ECHO) or multigated acquisition scan (MUGA) indicative of left ventricular ejection fraction (LVEF) ≤45%.
• Pulmonary function test of forced expiratory volume in the first second (FEV1) ≤60% in subjects with a prolonged history of cigarette smoking (e.g. ≥20 pack-year smoking history).
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia, psychiatric illness, or social situations that would limit compliance with study requirements.
• Subjects with infection requiring treatment, including but not limited to active tuberculosis, COVID-19, known HIV positive subjects or subjects with clinically active hepatitis A, B and C.
• Untreated or symptomatic brain metastasis.
• History of organ transplantation or allogeneic stem cell transplantation.
• Known uncontrolled diabetes, pulmonary fibrosis, interstitial lung disease, acute lung disease or liver failure.
• Previous use of any gene therapy product.

Sponsors & Collaborators

• Athenex, Inc.: lead

Study Officials

• Carlos Becerra, MD

  Baylor University Medical Cancer Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: open-label, multi-site, "3+3" dose escalation study

Study Record Dates

• First Submitted: March 1, 2021
• First Posted: May 7, 2021
• Study Start: August 11, 2021
• Primary Completion: October 1, 2022
• Study Completion: December 1, 2024
• Last Updated: September 2, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share