Clinical trial NCT06951425: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Solid Tumors
Lead sponsor: Shanghai Tongji Hospital, Tongji University School of Medicine
Sponsor class: OTHER
Collaborators: name: ThinkingBiomed
First posted: 2025-04-30
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


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.

Primary outcomes:
measure: Safety：Incidence of Dose Limiting Toxicity (DLT)
timeFrame: 28 days after the first TH-CART-027 infusion.
measure: Safety：Incidence and severity of adverse events (AEs)
timeFrame: Six months post CAR-T cells infusion.
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 12 and 24 months post CAR-T cells infusion.
measure: Objective response rate (ORR)
timeFrame: 3 months post CAR-T cells infusion.
measure: Progression Free Survival (PFS)
timeFrame: 1 year post CAR-T cells infusion.
measure: Disease Control Rate (DCR)
timeFrame: 1 year post CAR-T cells infusion
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Tongji Hospital, Tongji University School of Medicine
Study officials:
References: