Phase I Clinical Study to Evaluate the Safety and Efficacy of IM83 CAR-T Cells for the Treatment of Relapsed or Refractory Osteosarcoma

Beijing Immunochina Medical Science & Technology Co., Ltd.1 site in 1 country9 target enrollmentJune 15, 2024

ConditionsRefractory Osteosarcoma Recurrent Osteosarcoma

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Refractory Osteosarcoma
Sponsor: Beijing Immunochina Medical Science & Technology Co., Ltd.
Enrollment: 9
Locations: 1
Primary Endpoint: Incidence of Treatment Related adverse events (AEs)
Status: Not Yet Recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study, a single-center, open, single-dose clinical study, was to evaluate the safety, tolerability, and pharmacokinetic profile of IM83 CAR-T cells in the treatment of patients with relapsed or refractory osteosarcoma

Detailed Description

This study is planned to enroll 9-18 patients with relapsed or refractory osteosarcoma in a modified "3+3" design for dose escalation, with three dose groups of 5×10\^8 cells, 1×10\^9 cells, and 2×10\^9 cells.3-6 subjects are planned to be enrolled in each dose group to assess their safety. Each dose group is planned to enroll 3-6 subjects to assess safety, and if the incidence of horizontal dose-limiting toxicity (DLT) is ≤1/6 within 28 days after transfusion in a dose group, the transfusion of cells from the next dose group can be initiated. This study will be divided into a screening period, a cell collection period, a chemotherapy pretreatment period, a return infusion and a follow-up period, and within 28 days of return infusion the investigator will assess whether a DLT (Dose limited toxicity) event has occurred to confirm the safety of this dose group.

Registry

clinicaltrials.gov

Start Date

June 15, 2024

End Date

June 15, 2026

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Beijing Immunochina Medical Science & Technology Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Age ≥ 16 years, both male and female;
•Subjects with a diagnosis of osteosarcoma of the extremity confirmed by pathohistologic examination;
•To enroll subjects with recurrent or refractory extremity osteosarcoma who have failed or are intolerant to first-line standard therapy and who are not candidates for radical surgery and/or localized therapy and who lack effective subsequent treatment.
•Standard treatment failure was defined as disease relapse or progression during or within 6 months of completion of treatment with first-line chemotherapeutic agents (including high-dose methotrexate, doxorubicin, cisplatin, isocyclophosphamide, etc.);
•Requirement of treatment intolerance: means that the subject is unable to continue the current effective systemic regimen due to the development of toxic side effects such as ≥ grade 3 vomiting, diarrhea, abdominal pain, myelosuppression, etc., and that refusal is not accepted for financial and personal reasons;
•The standard treatment received by the subject must be in accordance with the Chinese Society of Clinical Oncology (CSCO) Guidelines for the Treatment of Bone and Soft Tissue Tumors, 2023 Edition;
•At least one measurable target lesion according to RECIST 1.1 criteria;
•Subjects must provide a tumor tissue sample (paraffin block or number of unstained sections meeting the testing requirements specified by the Institute) within 2 years that meets the requirements to be tested by immunohistochemistry for GPC3 and CD40 and needs to be positive for GPC3 expression;;
•Karnofsky functional status score ≥60;
•Expected survival ≥ 12 weeks;

Exclusion Criteria

•Presence of brain metastases;
•Subjects who have previously received or are awaiting an organ transplant;
•Toxicity due to prior therapy not stabilized or recovered to ≤ grade 1 (except in cases judged by the investigator to be not clinically significant);
•Autoimmune diseases requiring systemic immunosuppressive therapy, such as systemic lupus erythematosus, rheumatoid arthritis, and ulcerative colitis, within 2 years prior to the start of screening;
•Use of any of the following medications or treatments during the designated time period prior to cell collection:
•Surgical treatment, interventional therapy, radiotherapy, ablation, and other localized treatments for the study disease within 4 weeks prior to cell collection;
•Subjects who have had major surgery or significant trauma within 4 weeks prior to cell collection, or who are expected to require major surgery during the study period;
•Immunotherapy with anti-PD1, PD-L1, etc. within 4 weeks prior to cell collection;
•Therapeutic doses of corticosteroids have been used within 3 days prior to cell collection. However, topical and inhaled steroids are permitted;
•Other untreated malignant tumors within the previous 5 years or concurrently, except cervical cancer in situ, basal cell carcinoma of the skin, and ductal carcinoma in situ of the breast;

Outcomes

Primary Outcomes

Incidence of Treatment Related adverse events (AEs)

Time Frame: Up to 28 days after CAR-T cell infusion

Incidence of Adverse Events and Abnormal Findings on Clinically Significant Laboratory Tests Associated with IM83 CAR-T Cell Therapy Within 28 Days of Infusion

Secondary Outcomes

Disease control rate (DCR)(At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion)
Progress free survival (PFS)(At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion)
Cmax (Peak Concentration)(Up to 28 days after CAR-T cell infusion)
AUC (Area Under Curve) 0-D28(Up to 28 days after CAR-T cell infusion)
AUC (Area Under Curve) 0-D90(Up to 90 days after CAR-T cell infusion)
Objective response rate (ORR)(At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion)
Duration of response (DOR)(At 28 days, 3 months and 6 months after CAR-T cell infusion)
Overall Survival (OS)(At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion)