IM83 Clinical Study of CAR-T Cell Therapy in Patients With Relapsed or Refractory Osteosarcoma

NCT06412458 | Not Yet Recruiting Phase 1

• 1 other identifier: IM83-002
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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

Conditions

Refractory Osteosarcoma; Recurrent Osteosarcoma

Keywords

IM83 CAR-T; Relapsed or refractory osteosarcoma

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment Related adverse events (AEs)

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

  Up to 28 days after CAR-T cell infusion

Secondary Outcomes (8)

• Objective response rate (ORR)

  At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion

• Disease control rate (DCR)

  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

• Progress free survival (PFS)

  At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion

• Overall Survival (OS)

  At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion

Study Arms (1)

IM83 CAR-T Cells

EXPERIMENTAL

After preconditioning with chemotherapy, IM83 CAR-T Cells will be evaluated

Biological: IM83 CAR-T Cells

Interventions

IM83 CAR-T Cells BIOLOGICAL

IM83 CAR-T Cells, 5×10\^8 cells, 1×10\^9 cells, and 2×10\^9 cells, treatment follows a lymphodepletion. Drug: Fludarabine Recommendation: 30 mg/m\^2 (D-5\~D- 3), determined by tumor burden at baseline. Drug: Fludarabine Recommendation: 30 mg/m\^2 (D-5\~D-3), determined by tumor burden at baseline. Drug: Cyclophosphamide Recommendation: 300 mg/ m\^2 (D-5\~D-3), determined by tumor burden at baseline.

IM83 CAR-T Cells

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Notes:
• 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; 4. At least one measurable target lesion according to RECIST 1.1 criteria; 5. 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;; 6. Karnofsky functional status score ≥60; 7. Expected survival ≥ 12 weeks; 8. Laboratory tests should meet at least the indicators specified below:
• )Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L; 2)Absolute lymphocyte cell count (LY) ≥ 0.6 x 10\^9/L; 3)Lymphocytes make up ≥10% of white blood cells; 4)Platelets ≥75 x 10\^9/L; 5)Hemoglobin ≥ 90 g/L; 6)Creatinine clearance ≥60 ml/min; 7)Serum bilirubin ≤ 1.5 times the upper limit of normal; if liver metastases are present, serum bilirubin ≤ 3.0 times the upper limit of normal; 8)Prolongation of prothrombinogen time ≤ 4s; 9)≤ 2.5 times the upper limit of normal for albumin transaminase (AST) and albumin transaminase (ALT); if liver metastases are present, ALT and/or AST ≤ 5.0 times the upper limit of normal; 9. Left ventricular ejection fraction was \>50%; 10. Oxygen saturation \>92% in the non-oxygenated state; 11. Women of childbearing potential who had a negative blood pregnancy test prior to the start of the trial and who agreed to use effective contraception for the duration of the trial up to the last follow-up visit; male subjects whose partners were of childbearing potential agreed to use effective contraception for the duration of the trial up to the last follow-up visit; 12. Vascular access is adequate for cell collection, and lines are available for subjects with existing central venous catheters; 13. I or my legal guardian/proxy agree to participate in this trial and sign the informed consent form.

You may not qualify if:

• 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;
• Previously treated with targeted GPC3 therapy (can be enrolled if still positive for GPC3 expression upon testing);
• Those who have previously received other cellular therapy or genetically modified cellular therapy, such as TCR-T therapy, CAR-T therapy, etc;
• Prior or clinically significant CNS disorders at screening, such as epilepsy, seizures, cerebrovascular disease (ischemia/hemorrhage/infarction), cerebral edema, reversible posterior leukoencephalopathy, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disorders, organic brain syndromes, or psychiatric disorders;
• Presence of chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), and clinically significant pulmonary function test abnormalities;
• Subjects assessed by the investigator as having a significant amount of plasmapheresis (e.g., pleural effusion, peritoneal effusion, pericardial effusion) that cannot be controlled with treatment;

Sponsors & Collaborators

• Beijing Immunochina Medical Science & Technology Co., Ltd.: lead
• Guangdong Provincial People's Hospital: collaborator

Study Sites (1)

Guangdong Provincial People's Hospital

Guangdong, Guangdong, 519041, China

Location

MeSH Terms

Conditions

Osteosarcoma; Recurrence

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Yu Zhang, PhD

  Guangdong Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yu Zhang, PhD

CONTACT

8620 83827812; luck_2001@126.com

Junhua Nie, PhD

CONTACT

8620 83827812; 329877102@qq.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2024
• First Posted: May 14, 2024
• Study Start: June 15, 2024
• Primary Completion: June 15, 2025
• Study Completion (Estimated): June 15, 2026
• Last Updated: May 14, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)