Phase I Study of TX103 CAR-T Cells in Participants With Advanced Solid Tumors
ConditionSolid Tumors
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-75
SponsorTcelltech Inc.
About this trial
This is a single-arm, open-label, Phase I study to evaluate the safety, tolerability, and antitumor activity of TX103 CAR-T cells in subjects with TX103-positive advanced solid tumors. The study also aims to explore the maximum tolerated dose (MTD) and determine the recommended Phase II dose (RP2D) of TX103 CAR-T cell therapy.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
1. Voluntary participation: Subjects must voluntarily participate in this clinical trial, fully understand and sign the informed consent form (ICF), and be willing and able to comply with all study procedures.
Intraperitoneal infusion cohort: limited to subjects with recurrent or metastatic ovarian cancer, fallopian tube cancer, primary peritoneal cancer, or other advanced solid tumors with peritoneal metastases confined to the peritoneal cavity.
Intravenous infusion cohort: subjects with advanced solid tumors regardless of peritoneal metastasis, preferably including head and neck squamous cell carcinoma, esophageal cancer, lung malignancies, triple-negative breast cancer, colorectal cancer, and mesenchymal-derived malignancies.
Intraperitoneal infusion cohort, Phase Ia: at least one evaluable lesion per RECIST 1.1;
Disqualifiers
Positive for HIV antibody or syphilis serologic test;
Positive for HBsAg or HBcAb with HBV DNA ≥ 2000 IU/mL;
Positive for HCV antibody with detectable HCV RNA;
Presence of other active viremia. 3. Known hypersensitivity, allergy, intolerance, or contraindication to TX103 CAR-T or any component of the study drugs (including fludarabine, cyclophosphamide, or tocilizumab), or history of severe allergic reactions.
Trial design
Design model
Single group
Treatments tested in this trial
Anti-B7-H3 Chimeric Antigen Receptor T-Cell (CAR-T Cell) Injection/TX103
Biological/VaccineTX103 CAR-T cells are autologous T cells genetically engineered to express a chimeric antigen receptor (CAR) targeting TX103-positive tumor cells. This therapy is designed to recognize and kill TX103-expressing malignant cells. TX103 CAR-T cells are administered either via intravenous (IV) infusion or intraperitoneal (IP) infusion, depending on the cohort. For dose-escalation cohorts (Phase Ia), a standard 3+3 design is used: 1. IV dose-escalation cohort: planned doses range from 1.0 × 10⁸ to 2.0 × 10⁹ CAR-T cells. 2. IP dose-escalation cohort: initiated sequentially after the IV cohort; starting dose is based on the safe and potentially efficacious dose from IV cohort, with planned escalation up to 4.0 × 10⁹ CAR-T cells. The Phase Ib expansion cohort administers TX103 CAR-T at the dose determined to be safe and potentially efficacious in Phase Ia, focusing on tumor types that showed preliminary signs of antitumor activity and meet clinical needs. TX103 CAR-T therapy is distinct fro
Treatment groups
85 Participants
are divided into 3 treatment groupsGroup A: IV Dose-Escalation CohortExperimental treatment 1 intervention
Group B: IP Dose-Escalation CohortExperimental treatment 1 intervention
Group C: Expansion Cohort (Phase Ib)Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Safety#Incidence and severity of adverse events (AEs)
To evaluate the possible adverse events after TX103 infusion, including the incidence, and severity of AEs.
Time frame
1 year post CAR-T cells infusion2
Safety#Incidence of Dose Limiting Toxicity (DLT)
Type, incidence, and severity of dose limiting toxicities (DLTs) within 28 days after the first TX103 infusion.
Time frame
28 days after the first TX103 infusion3
The maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of TX103
Time frame
From first dose of TX103 until the end of Dose Limiting Toxicity (DLT) observation period (typically 28 days post-infusion for each dose).Secondary outcomes
1
Progression Free Survival (PFS)
To evaluate the time from the start of TX103 therapy to disease progression (according to RICIST1.1 criteria) or death from any cause, whichever occurs first.
Time frame
1 year post CAR-T cells infusion2
Disease Control Rate (DCR)
To evaluate the proportion of subjects who achieved CR/PR/SD in the best overall response according to RICIST1.1 criteria.
Time frame
1 year post CAR-T cells infusion.3
Overall survival (OS)
The proportion of subjects who have survived for more than 6 and 12 months since the first infusion.
Time frame
6 and 12 months post CAR-T cells infusion4
Objective response rate (ORR)
To evaluate the proportion of subjects who achieved CR/PR in the best response condition according to RICIST1.1 criteria.
Time frame
1 year post CAR-T cells infusionOther outcomes
1
The immunogenicity of TX103
Drug antibody (ADA) positive rate after infusion of TX103.
Time frame
Up to 12 months2
The positive rate of replication competent lentivirus tests.
Detect replication competent lentivirus (RCL)
Time frame
Up to 15 years.3
Peak Concentration (Cmax) of TX103 CAR gene.
Peak Concentration (Cmax) of TX103 CAR gene.
Time frame
Up to 12 months4
Area under the concentration versus time curve (AUC) of TX103 CAR-T cells.
Area under the concentration versus time curve (AUC) of TX103 CAR-T cells.
Time frame
Up to 12 monthsSponsors and contacts
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Source ClinicalTrials.gov