An Exploratory Clinical Study of the Efficiency and Safety of TH027 in the Treatment of Relapsed/Refractory Solid Tumors

Official title

A Phase l, Open-Label, Dose-escalation Study to Evaluate the Safety, Tolerability and Antitumor Activity of TH027 CAR-T Cells (TH-CART-027) in Subjects With Relapsed or Refractory Solid Tumors

Overview

This is a Phase l, Open-Label, Dose-escalation Study to Evaluate the Safety, Tolerabilityand Antitumor Activity of TH027 CAR-T Cell lnjection (TH-CART-027) in Subjects With Relapsed or Refractory Solid Tumors.

Interventions

• Drug TH-CART-027
  3+3 dose escalation design: Dose Level 1: 0.3×10\^6 CAR+ T cells /kg; Dose Level 2: 1.0×10\^6 CAR+ T cells /kg; Dose Level 3: 3.0×10\^6 CAR+ T cells /kg

Primary outcome measures

• Safety：Incidence of Dose Limiting Toxicity (DLT) [Time frame: 28 days after the first TH-CART-027 infusion.]
• Safety：Incidence and severity of adverse events (AEs) [Time frame: Six months post CAR-T cells infusion.]

Secondary outcome measures (4)

• Overall survival (OS) [Time frame: 12 and 24 months post CAR-T cells infusion.]
• Objective response rate (ORR) [Time frame: 3 months post CAR-T cells infusion.]
• Progression Free Survival (PFS) [Time frame: 1 year post CAR-T cells infusion.]
• Disease Control Rate (DCR) [Time frame: 1 year post CAR-T cells infusion]

Eligibility criteria

Inclusion criteria

• 1.The patients were aged from 18 to 75 years old (including the cut-off value), and the gender was not limited;
• 2.The expected survival time was more than 12 weeks;
• 3.ECOG score was 0-2;
• 4.One of the following tumor types was confirmed by pathology: osteosarcoma, neuroblastoma, gastric cancer or lung cancer, and the positive rate of CD276 expression in tumor tissue was more than 30% by immunohistochemistry;
• 5.Patients with ineffective standard treatment methods (such as postoperative recurrence, chemotherapy, radiotherapy, and progression after targeted drugs);
• 6.According to RECIST 1.1, there was at least one measurable lesion (the longest diameter of solid lesion >=10 mm, or the short diameter of lymph node lesion >=15 mm);
• 7.The function of main organs was normal (white blood cell count >= 3 × 10\^9 / L, neutrophil count >= 1.5 × 10\^9 / L, hemoglobin >= 8.5g/dl, platelet count >= 80 × 10\^9 / L and lymphocyte count at 1 × 10\^9 / L (including) \~ 4 × 10\^9 / L (inclusive);
• 8.The liver and kidney function and cardiopulmonary function meet the following requirements:
• Urea and serum creatinine <= 1.5 × ULN；
• Left ventricular ejection fraction >= 50%;
• Baseline oxygen saturation >= 94%;
• Total bilirubin <= 1.5 × ULN； ALT and AST <= 2.5 × ULN；
• 9.The patient or legal representative can fully understand the significance and risk of this trial and has signed the informed consent.

Exclusion criteria

• 1.Patients with history of immune deficiency or autoimmune diseases (including but not limited to rheumatoid arthritis, systemic lupus erythematosus, vasculitis, multiple sclerosis, insulin-dependent diabetes, etc.); Patients with graft-versus-host disease (GVHD) or need immunosuppressive agents;
• 2.There was a history of other second malignancies in 5 years before screening;
• 3.Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) were positive, and the peripheral blood HBV DNA titer was not within the normal reference value; HCV antibody and HCV RNA in peripheral blood were positive; HIV antibody positive patients; Syphilis was positive;
• 4.Severe heart disease: including but not limited to unstable angina pectoris, myocardial infarction (within 6 months before screening), congestive heart failure (NYHA classification >= III), severe arrhythmia;
• 5.Unstable systemic diseases judged by researchers: including but not limited to severe liver, kidney or metabolic diseases requiring drug treatment;
• 6.Within 7 days before screening, there were active or uncontrollable infections requiring systemic treatment (except mild urogenital infection and upper respiratory tract infection);
• 7.Pregnant or lactating women, female subjects who plan to conceive within one year after cell transfusion, or male subjects whose partners plan to conceive within one year after cell transfusion;
• 8.Patients who had received CAR-T therapy or other gene modified cell therapy before screening;
• 9.The subjects who were receiving systemic steroid treatment within 7 days before the screening or who needed long-term systemic steroid treatment (except inhalation or local use) were determined by the researchers;
• 10.The ascites increased gradually after 2 weeks of conservative treatment (such as diuresis, sodium restriction, excluding ascites drainage);
• 11.According to the judgment of the researcher, it does not conform to the situation of cell preparation;
• 12.Other researchers think that it is not suitable for inclusion.

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

• Shanghai Tongji Hospital, Tongji University School of Medicine — Shanghai

Identifiers

NCT: NCT06951425 · TH027-ST001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗