A Safety and Efficacy Study Evaluating CTX112 in Subjects With Relapsed or Refractory B-Cell Malignancies

Study Overview
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Brief Summary
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This is an open-label, multicenter, Phase 1/2 study evaluating the safety and efficacy of CTX112™ in subjects with relapsed or refractory B-cell malignancies.

Detailed Description
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This is an open-label, multi-center Phase 1/2 study of CTX112 in subjects with relapsed/refractory B cell malignancies. CTX112 is an is allogeneic CD19-directed chimeric antigen receptor (CAR) T cell immunotherapy comprised of allogeneic T cells that are genetically modified ex vivo using CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats/ CRISPR associated protein 9) gene editing components (single guide RNA and Cas9 nuclease).

Official Title
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A Phase 1/2, Open-Label, Multicenter, Dose Escalation and Cohort Expansion Study of the Safety and Efficacy of Anti-CD19 Allogeneic CRISPR-Cas9-Engineered T Cells (CTX112) in Subjects With Relapsed or Refractory B Cell Malignancies

Conditions
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Mantle Cell Lymphoma, B-cell Lymphoma, Non-Hodgkin Lymphoma, B-cell Malignancy, Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL), Follicular Lymphoma, Marginal Zone Lymphoma, Large B-cell Lymphoma

Intervention / Treatment
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* Biological: CTX112


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Age ≥18 years. Refractory or relapsed B cell malignancy. Eastern Cooperative Oncology Group performance status 0 or 1. Adequate renal, liver, cardiac and pulmonary organ function. Female subjects of childbearing potential and male subjects must agree to use acceptable method(s) of contraception from enrollment through at least 12 months after CTX112 infusion. Key Exclusion Criteria: Prior allogeneic hematopoietic stem cell transplant (HSCT). Active or history of central nervous system (CNS) involvement by malignancy. History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement. Presence of bacterial, viral, or fungal infection that is uncontrolled or requires IV anti-infectives. Active HIV, hepatitis B virus or hepatitis C virus infection. Previous or concurrent malignancy, except basal cell or squamous cell skin carcinoma, adequately resected and in situ carcinoma of cervix, or a previous malignancy that was completely resected and has been in remission for ≥5 years. Use of systemic anti-tumor therapy or investigational agent within 14 days or 5 half-lives, whichever is longer, of enrollment. Primary immunodeficiency disorder or active autoimmune disease requiring steroids and/or other immunosuppressive therapy. Women who are pregnant or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CTX112<br>Administered by IV infusion following lymphodepleting chemotherapy. | Biological: CTX112<br>* CTX112 (CD19-directed T-cell immunotherapy comprised of allogeneic T cells genetically modified ex vivo using CRISPR-Cas9 gene editing components)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 (Dose Escalation): Incidence of adverse events, defined as dose-limiting toxicities |  | From CTX112 infusion up to 28 days post-infusion | 
| Phase 2 (Cohort Expansion): Objective response rate |  | From CTX112 infusion up to 60 months post-infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response | Duration of Response (DOR) will only be reported for subjects who have had CR/PR events | From date of first objective response of complete response (CR)/partial response (PR) until date of disease progression or death due to any cause, assessed up to 60 months | 
| Duration of Clinical Benefit (DOCB) |  | From date of first objective response of CR/PR until the relapse or death that followed the last response, assessed up to 60 months | 
| Progression Free Survival |  | From date of CTX112 infusion until date of disease progression or death due to any cause, assessed up to 60 months | 
| Overall Survival |  | From date of CTX112 infusion until date of death due to any cause, assessed up to 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAR T, Non-Hodgkin Lymphoma (NHL), Lymphoma, Allogeneic