MAGE-A4-directed TCR-T in the Treatment Amongst Subjects With Advanced Solid Tumors

Official title

A Single-arm, Open-label, Dose Exploratory Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Autologous Humanized MAGE-A4-directed T Cell Receptor Engineered T Cell (JWTCR001) in Patients With Advanced Solid Tumors

Overview

A single-arm, open-label, dose exploratory study to evaluate the safety, efficacy, and pharmacokinetics of autologous humanized anti-MAGE-A4 T cell receptor-engineered T cell (TCR-T) in advanced solid tumors.

Detailed description

This study is a single-arm, open-label, dose escalation/dose regimen finding study to assess the safety and pharmacokinetics of T-cell receptor-engineered T cell (TCR-T) targeting melanoma-associated antigen-4 (MAGE-A4) and to obtain the preliminary efficacy results in subjects who have been diagnosed with advanced solid tumors with positive MAGE-A4 expression and refractory to prior standard systemic treatments.

Interventions

• Drug TCR-MAGE-A4 T-Cells
  * Preconditioning with fludarabine, cyclophosphamide, based chemotherapy regimen at sub-clinical doses * MAGE-A4-directed T cell receptor-engineered T Cells

Primary outcome measures

• Rate of dose-limiting toxicities (DLTs) [Time frame: 28 days]
• Rate and severity of adverse events (AEs) and severe adverse events (SAEs) [Time frame: 2 years]
• Rate and severity of clinically-significant abnormalities in laboratory testings [Time frame: 2 years]

Secondary outcome measures (8)

• Copy number of the vector transgene of JWTCR001 in peripheral blood [Time frame: 2 years]
• MAGE-A4 specific TCR+ T Cell concentration of JWTCR001 in peripheral blood [Time frame: 2 years]
• Antitumor efficacy-Progression-free survival (PFS) [Time frame: 2 years]
• Antitumor efficacy-Duration of response (DOR) [Time frame: 2 years]
• Antitumor efficacy-Time to response (TTR) [Time frame: 2 years]
• Antitumor efficacy-Overall survival (OS) [Time frame: 2 years]
• Antitumor efficacy-Objective response rate (ORR) [Time frame: 2 years]
• Antitumor efficacy-Disease control rate (DCR) [Time frame: 2 years]

Eligibility criteria

Inclusion criteria

• 18-75 year-old, male or female
• Voluntarily willing to participate in the study and sign the written informed consent form
• Life expectation ≥12 weeks
• European Cooperative Oncology Group (ECOG) ≤1 at screening, 24 hours prior to apheresis (APH), lymphodepletion (LD), and infusion
• Histologically-confirmed recurrent/metastatic advanced solid tumors
• Radiologically-confirmed progression disease after at least one prior line of systematic treatment and no available standard of care at screening, judged by investigators
• Fresh or formalin-fixed paraffin-embedded (FFPE) samples, immunohistochemistry (IHC)-stained MAGE-A4 positive
• Human leukocyte antigen (HLA)-A\*02 allele matched
• Per response evaluation criteria in solid tumors (RECIST) version 1.1, at least one measurable lesion
• Adequate organ functions
• Adequate venous access for APH
• Non-hematological adverse events induced by previous treatment must have recovered to Grade ≤1 according to Common Terminology Criteria for Adverse Events (CTCAE), except for alopecia and peripheral neuropathy
• Women of childbearing potential must agree to use an effective and reliable contraceptive method during 28 days prior to lymphodepletion to 1 year post infusion; Male patients who have not undergone vasectomy and have sexual activity with women of childbearing potential must agree to the use of a barrier contraceptive method since lymphodepletion to 1 year post infusion, and sperm donation is prohibited during the study
• Women of childbearing potential must have negative serum human chorionic gonadotropin β (β-hCG) test result at screening and 48 hours prior to lymphodepletion

Exclusion criteria

• Pregnant or lactating women
• Human immunodeficiency virus (HIV) serology positive, or active hepatitis B virus (HBV)/hepatitis C virus (HCV)/Syphilis/Tuberculosis/ Coronavirus disease 2019 (COVID-19)
• Central nerve system (CNS) metastasis must have received treatment and been neurologically stable for ≥2 months, not requiring anti-seizure medications and off steroids for ≥ 1 month prior to APH
• Another primary malignancy within 3 years (with some exceptions for completely-resected early-stage tumors)
• Subjects with extensive metastases, or more rapid tumor progression prior to lymphodepletion in comparison to screening, etc. which might not be appropriate for further study treatment judged by the investigators
• Systematic autoimmune disorders requiring long-term systematic treatment
• Previously treated with any genetically engineered modified T cell therapy or other cell and gene therapy (CGT)
• History of organ transplant
• Uncontrolled or active infection within 72 hours prior to screening, APH, LD, or within 5 days prior to infusion
• Subjects with other serious diseases that may restrict them from participating in this study
• Clinically significant CNS disorders, such as epilepsy, stroke, Parkinson disease, etc
• Grade ≥ 2 hemorrhage within 30 days prior to screening, or in need of longterm anticoagulants
• Active digestive ulcer or gastrointestinal (GI) bleeding within 3 months prior to screening
• Not satisfying wash-out period for APH
• Previously allergic or intolerable to JWTCR001 or its components
• Unable or unwilling to comply with the study protocol, judged by the investigators
• Other situations implying that the subject might not be appropriate to participate in the study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Department of GI Oncology,Peking University Cancer Hospital — Beijing

Identifiers

NCT: NCT06170294 · JWTCR001001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗