Overview
This is a open-Label, dose-escalation study to evaluate the safety, tolerability and antitumor activity of DIT309 in subjects with advanced bone and soft tissue sarcomas.The study also plan to explore the Maximum Tolerated Dose (MTD) and determine the Recommended Phase II Dose (RP2D) of the CAR-T cell therapy.
Description
Subjects will be enrolled to receive DIT309 via intravenous infusion. Patients will be administered DIT309 on Day 1 of each 28-day treatment cycle, followed by a 28-day observation period.
The study will include three escalating dose levels, utilizing a traditional 3+3 dose escalation design. Each dose level will enroll 3 to 6 patients. Dose-limiting toxicities (DLTs) will be assessed during the first treatment cycle to evaluate the safety and tolerability of DIT309.
Eligibility
Inclusion Criteria:
- Voluntarily agrees to participate in the clinical trial; is fully informed about the study and has signed the informed consent form (ICF); is willing and able to comply with all study procedures.
- Male or female patients aged ≥8 weeks.
- Histologically confirmed diagnosis of advanced bone and soft tissue sarcoma, who have failed or are intolerant to prior standard therapies.
- At least one measurable lesion as defined by RECIST version 1.1.
- Tumor tissue demonstrates positive expression for the target antigen according to the protocol-defined criteria.
- ECOG performance status of 0-1 within 24 hours prior to leukapheresis and prior to lymphodepletion.
- Life expectancy of more than 6 months.
- Adequate venous access for leukapheresis, with no contraindications for the procedure.
- Laboratory parameters must meet the following criteria:
- Hematologic function: WBC ≥ 3.0 × 10⁹/L; Hemoglobin ≥ 8.0 g/dL; ANC ≥ 1.5 × 10⁹/L; Platelets ≥ 75.0 × 10⁹/L
- Renal function: Serum creatinine ≤ 1.5 × upper limit of normal (ULN)
- Hepatic function: ALT and AST ≤ 2.5 × ULN (≤ 5.0 × ULN for subjects with liver metastasis)
- Total bilirubin ≤ 2.0 × ULN (excluding patients with Gilbert's syndrome, defined as persistent or recurrent unconjugated hyperbilirubinemia without evidence of hemolysis or hepatic pathology)
- Coagulation: Without anticoagulation therapy, PT, APTT, or INR ≤ 1.5 × ULN
- Negative pregnancy test for female subjects of childbearing potential
- Subjects of childbearing potential must agree to use effective contraception from the date of signing the informed consent through 6 months after the last infusion.
Exclusion Criteria:
- Pregnant or breastfeeding women
- Viral infections:
- Positive serology for HIV antibodies or syphilis
- Positive HBsAg or HBcAb with HBV DNA above the lower limit of detection in peripheral blood
- Positive HCV antibody with detectable HCV RNA in peripheral blood
- Medical history and comorbidities:
- Known hypersensitivity to DIT309 cells or any component of the investigational products (including fludarabine, cyclophosphamide, or trastuzumab), or history of severe allergic reactions
- Known active autoimmune diseases (e.g., Crohn's disease, systemic lupus erythematosus); subjects with vitiligo or childhood asthma in complete remission and not requiring treatment in adulthood may be eligible; subjects requiring medical intervention such as bronchodilators for asthma are not eligible
- Currently receiving systemic immunosuppressive therapy or anticipated need for long-term immunosuppression during the study (topical, inhaled, or intranasal corticosteroids used intermittently are allowed)
- Prior exposure to any gene-modified T cell therapy (e.g., CAR-T or TCR-T) or any form of gene therapy\*
- History of uncontrolled neurological or psychiatric disorders that may increase the risk of participation or interfere with study results in the investigator's opinion, including but not limited to epilepsy, dementia, or major depression
- Untreated or symptomatic CNS or leptomeningeal metastases
- Unresolved toxicities from prior treatment that have not recovered to Grade ≤1 per CTCAE v5.0 (except for toxicities deemed not to pose safety risk by the investigator, such as alopecia, Grade 2 peripheral neuropathy, or hypothyroidism managed with replacement therapy)
- History of other primary solid malignancies
- Major surgery or significant trauma within 1 month prior to leukapheresis
- Any serious or uncontrolled comorbidity that, in the investigator's opinion, may increase risks associated with study participation or investigational drug administration, including but not limited to: cardiovascular or cerebrovascular disease, renal insufficiency, pulmonary embolism, coagulation disorders requiring long-term anticoagulation, active or uncontrolled infections requiring systemic treatment.
