CCT301-38 CAR-T in Patients With Relapsed or Refractory AXL Positive Sarcomas

Study Overview
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Brief Summary
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This clinical study is to investigate the safety and tolerability of CCT301-38 CAR modified autologous T cells (CCT301-38) in subjects with relapsed or refractory AXL positive sarcomas

Detailed Description
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This study is an open label, single-center Phase I dose escalation trial to assess the safety, tolerability, DLT and MTD of CCT301-38 cell therapy in patients with AXL positive relapsed or refractory sarcomas. Subjects that meet inclusion criteria with positive AXL biopsy (IHC 1+ or greater in ≥50% tumor cells) will receive CCT301-38 according to the 3+3 dose escalation design.

Official Title
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A Phase I Trial to Assess Safety, Tolerability and Anti-tumor Activity of Autologous T Cell Modified Chimeric Antigen Receptor (CAR) (CCT301-38) in Patients With Relapsed or Refractory AXL Positive Sarcomas

Conditions
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SAR

Intervention / Treatment
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* Biological: CCT301-38


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with willingness to be in the study and follow all study procedures, and capable of providing informed consent Male or female aged 18-70 years; Patients with unresectable, locally advanced or metastatic relapse/refractory sarcomas that have failed at least the front line standard treatment confirmed by histology or cytology; At least one measurable lesion, i.e. the length of non-lymph node lesions examined according to CT cross-sectional scanning or magnetic resonance imaging (MRI), or the short diameter of the lymph node lesions is ≥15 mm according to RECIST 1.1, and the FDG PET signal from the measurable lesion is > 3 SUV; Tumors with AXL positive (IHC 1+ or greater) in ≥50% of all tumor cells. A new biopsy is required if the sample is over one year. ECOG Performance Status 0-1; Expected survival greater than 12 weeks; Adequate organ and hematopoietic system functions to meet the following requirements: Hemoglobin (HGB) s 90 g/L, no blood transfusions within two weeks; White blood cell (WBC) count≥2.5×109/L； Absolute Neutrophil Count (ANC) ≥1.5×109/L; Platelet (PLT) count ≥80×109/L; Total bilirubin (TBIL) ≤3.0ng/dL or ≤5 ULN; ALT and AST ≤5 ULN; for liver metastasis, ALT and AST ≤5 ULN Creatinine (Cr) ≤1.5 x ULN; or creatinine removal rate (CrCl) ≥50 mL/min; PT: INR < 1.7 or extended PT to normal value < 4s Normal language, recognition and consciousness assessed by investigator during screening phase; Capable of receiving treatment and follow-up, including treatment in the clinical center; Exclusion Criteria: Females with pregnancy or in lactation period; Subjects with active hepatitis B, or active hepatitis C. Subjects with undetectable HBV DNA or HCV RNA after anti-virus treatment can be enrolled; HIV positive; Other active infections of clinical significance; Subjects with the following previous or accompanying diseases: • Subjects diagnosed as severe autoimmune diseases that require long term (more than 2 months) treatment with systemic immunosuppressants (steroids), or diseases with immune-mediated symptoms, including ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus (SLE), and autoimmune vasculitis (e.g. Wegena granuloma); Patients with previous diagnosis as motor neuron disease caused by autoimmunity; Patients previously suffered from toxic epidermal necrolysis (TEN) Patients with any mental illness, including dementia, mental changes, which may cause difficulties understanding the informed consent and related questionnaires; Patients with serious uncontrollable diseases, which may interfere with the therapies in this study; Patients with other active malignancies in the past 5 years excluding those with completely cured basal or squamous skin cancers, superficial bladder cancers or primary breast cancers without need of follow-up treatment; Subjects receiving systemic steroids or steroid inhalants; Patients who have received tumor immunotherapy (including monoclonal antibody against PD-1, PD-L1, PD-L2, CD137 or CTLA-4, or cell therapy) in the past 4 weeks; Subjects allergic to immunotherapies or related drugs; Patients with metastatic lesions in meninges or central nervous system, or clear evidence of central nervous system diseases with continuous significant symptoms in the last 6 months; Patients with NYHA class II heart failure, or hypertension incontrollable by standard care, or medical history of myocarditis, or heart attack within a year; Subjects who have received or are going to receive organ transplantation; Patients with active bleeding; Patients with incontrollable pleural or abdominal fluid that needs clinical treatment or intervention; Patients as determined by the investigators to be inappropriate for the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CCT301-38<br>To determine the safety, tolerability, DLT and MTD of CCT301-38 cell therapy in patients with AXL-positive relapsed or refractory sarcomas. | Biological: CCT301-38<br>* Blood will be collected from subjects to isolate peripheral blood mononuclear cells for the production of CCT301-38. Subjects will receive the conditioning chemotherapy regimen of cyclophosphamide and fludarabine for lymphodepletion followed by a single or multiple dose of CCT301-38 via intravenous injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLT | To assess the safety and tolerability of CCT301-38 cell therapy for patients with AXL-positive (IHC 1+ or greater in ≥50% tumor cells) relapsed or refractory sarcomas. | 28 days following infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Proportion of subjects with the best overall response (BOR) of subjects with PR (partial response) and CR (complete response) as determined by local investigator using RECIST 1.1 | Up to 52 weeks | 
| DCR | Disease control rate: The proportion of subjects with CR (complete response), PR (partial response) or SD (stable disease lasting over 6 months) as determined by local investigator using RECIST 1.1. | Up to 52 weeks | 
| DOR | Duration of response: The duration of time from record of response to first progression of disease as determined by RECIST 1.1 or death date not relevant to disease progression. | Up to 52 weeks | 
| PFS | Progression free survival: The time of disease progression by RECIST 1.1 or death since cell infusion. | Up to 52 weeks | 
| TEAE | Number, severity and duration of treatment of emergent adverse events (TEAEs) that occur during treatment according to NCI-CTCAE v 5.0. | Up to 52 weeks | 
| PK | The % of patients with detectable CCT301-38 cells in peripheral blood. [Time Frame: Up to 52 weeks] | Up to 52 weeks | 
| Biomarker | To evaluate the correlation of AXL biopsy score to ORR. [Time Frame: Up to 52 weeks] | Up to 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sarcoma, AXL, CAR-T, CCT301-38, sarcoma, CAR-T, CCT301-38