A Study of EXP039 Treatment in Subjects With r/r NHL Subjects

Study Overview
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Brief Summary
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This is a single-center, non-randomized study to evaluate the safety and efficacy of EXP039 in relapsed and/or refractory NHL patients.

Detailed Description
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The study will include the following sequential phases: Screening, Apheresis, Baseline, Pre-Treatment (Cell Product Preparation, Lymphodepleting Chemotherapy), EXP039 infusion and Follow-up Visit.

Official Title
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A Phase 1 Study Evaluating Safety and Efficacy of EXP039 Treatment in Subjects With Relapsed and/or Refractory NHL

Conditions
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Non-Hodgkin's B-cell Lymphoma

Intervention / Treatment
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* Biological: CD19/CD20-directed CAR-T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient volunteered to participate in the study and signed the Informed Consent Age ≥18 years old ≤70 Years old, male or female Expected survival ≥ 12 weeks ECOG score 0-2 CD19 or CD20 positive B-NHL confirmed by cytology or histology according to WHO2016 criteria Patients with a clear diagnosis of relapsed and/or refractory B-NHL, including DLBCL, FL and MCL For CD20-positive subjects, they should have received at least one regimen containing anti-CD20-targeted therapy (such as rituximab). If they do not complete the regimen due to intolerance, the cause of intolerance should be recorded No contraindications of apheresis At least one measurable lesion according to Lugano 2014 criteria Adequate organ function and adequate bone marrow reserve Exclusion Criteria: Malignant tumors other than B-NHL within 5 years prior to screening, except cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery, and breast ductal carcinoma in situ after radical surgery Active HIV, HBV, HCV or treponema pallidum infection Any instability of systemic disease, including but not limited to active infection (except local infection), severe cardiac, liver, kidney, or metabolic disease need therapy Female subjects who have been pregnant or breastfeeding, or who plan to conceive during or within 1 year after treatment, or male subjects' partner plans to conceive within 1 year after their cell transfusion Active or uncontrolled infections requiring systemic treatment within 14 days before enrollment Patients who have been previously infected with tuberculosis Administered Corticosteroids and/or other immunosuppressants within 7 days before apheresis. and 5 days before the infusion of EXP039 Patients with central nervous system involvement Any systemic antitumor therapy performed within 2 weeks before enrollment Previous use of any CAR T cell product or other genetically modified T cell therapy

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: Autologous EXP039 administered by intravenous (IV) infusion<br>Autologous EXP039 administered by intravenous (IV) infusion | Biological: CD19/CD20-directed CAR-T cells<br>* Autologous 2nd generation CD19/CD20-directed CAR-T cells, single infusion intravenously<br>* Other names: EXP039;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of study related adverse events | Incidence and severity of Treatment emergent adverse events | 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum concentration (Cmax) of EXP039 in the peripheral blood | Detect CAR-T copies number by qPCR | up to 12 months | 
| Time to maximum concentration (Tmax) of EXP039 in the peripheral blood | Detect CAR-T copies number by qPCR | up to 12 months | 
| Tlast of EXP039 in the peripheral blood after infusion | Detect CAR-T copies number by qPCR | up to 12 months | 
| AUC0h-28d of EXP039 in the peripheral blood | Detect CAR-T copies number by qPCR | 4 weeks | 
| Objective response rate (ORR) | Complete response (CR) rate plus partial response (PR) rate by Lugano 2014 criteria | 4 weeks, 12 weeks, 6 months, 9 months, 12 months | 
| Duration of response (DOR) | The time from the date of first response (PR or better) until the date of disease progression after EXP039 infusion | up to 12 months | 
| Progression-free survival (PFS) | The time from EXP039 infusion to the date of progression as assessed by Lugano 2014 criteria or death | 4 weeks, 12 weeks, 6 months, 9 months, 12 months | 
| Overall survival rate (OSR) | The time from EXP039 infusion to the date of death | 12 weeks, 6 months, 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD19/CD20-directed CAR-T cells