Study Evaluating SC291 in Subjects With r/r B-cell Malignancies (ARDENT)

Study Overview
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Brief Summary
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SC291-101 is a Phase 1 study to evaluate SC291 safety and tolerability, anti-tumor activity, cellular kinetics, immunogenicity, and exploratory biomarkers.

Detailed Description
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This is an open-label, single arm, Phase 1, first-in-human (FIH) study to evaluate the safety and tolerability of SC291 administered intravenously (IV) following a standard lymphodepleting chemotherapy regimen of cyclophosphamide and fludarabine in subjects with NHL or CLL who have received two or more prior systemic treatments per standard of care (or after autologous stem cell transplant [ASCT] for NHL). This study will be conducted in 2 parts. Phase 1a: dose finding using a 3+3 design in subjects with NHL or CLL. Phase 1b: dose expansion to further evaluate safety and efficacy at the RP2D in subjects with LBCL and CLL.

Official Title
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A Phase 1 Study Evaluating SC291, a Hypoimmune, Allogeneic CD19-directed CAR T Cell Therapy, in Relapsed and/or Refractory B-cell Malignancies (ARDENT)

Conditions
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Non Hodgkin Lymphoma, Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: SC291


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects aged 18-75 years at the time of signing informed consent. Diagnosis of NHL (WHO 2016 criteria) or CLL (iwCLL criteria), including: Large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL) not otherwise - - specified (including DLBCL arising from indolent lymphoma), primary mediastinal large -- - B-cell lymphoma, high grade B-cell lymphoma, follicular lymphoma grade 3B Follicular lymphoma (dose escalation only except for follicular lymphoma grade 3B) Marginal zone lymphoma (dose escalation only) Mantle cell lymphoma (dose escalation only) CLL or SLL Relapsed/refractory disease after at least 2 prior systemic regimens per standard of care or after autologous stem cell transplant ECOG performance status of 0 or 1. At least one measurable lesion per Lugano Classification (NHL); CLL subjects must meet iwCLL treatment criteria Life expectancy ≥12 weeks Exclusion Criteria: Prior anti-CD19 therapy including CD19-directed CAR T treatment or other CD19-directed antibody or cell therapy (e.g., NK cell). (Part 2 dose expansion only - prior approved CD19-directed CAR T therapy required) History of primary central nervous system (CNS) lymphoma or presence of CNS metastases Systemic anticancer therapy (including platinum-based chemotherapies and I/O therapies) or radiotherapy within 14 days of SC291 (28 days for biologics) Autologous HSCT within 6 weeks of treatment with SC291 (or allogeneic HSCT at any time). Active autoimmune disease or any other diseases requiring immunosuppressive therapy or corticosteroid therapy (defined as >20 mg/day prednisone or equivalent). History or presence of cardiac or CNS disorders as defined in the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: SC291 Plus Chemotherapy Regimen<br>A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment with SC291 | Drug: SC291<br>* SC291 is an allogeneic CAR-T cell therapy<br>* Other names: Fludarabine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate safety and tolerability of SC291 | Safety and Tolerability: Proportion of subjects experiencing adverse events and dose-limiting toxicities | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate preliminary anti-tumor activity of SC291 | Preliminary anti-tumor activity: Proportion of subjects with an objective response (including partial response or complete response) | 24 months | 
| Evaluate cellular kinetics and persistence of SC291 | Cellular kinetics-related parameters evaluated by CAR T cell copy number | 24 months | 
| Evaluate cellular kinetics and persistence of SC291 | Cellular kinetics related peak (Cmax) in peripheral blood | 24 months | 
| Evaluate cellular kinetics and persistence of SC291 | Area under the concentration time curve (AUC) in peripheral blood | 24 months | 
| Evaluate host immunogenicity to SC291 | Incidence of anti-CD19-directed CAR antibodies | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Large B cell lymphoma, CAR T Cell Therapy, Mantle cell lymphoma, Indolent follicular lymphoma, Marginal zone lymphoma, High-grade B cell lymphoma, Primary mediastinal B cell lymphoma, Diffuse large B cell lymphoma, Non-Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia, Allogeneic, Hypoimmune, CD19