A Safety and Efficacy Study Evaluating CTX131 in Adult Subjects With Relapsed or Refractory Solid Tumors

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 CTX131™ in subjects with relapsed or refractory solid tumors.

Detailed Description
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An open-label, multi-center Phase 1/2 study of CTX131 in subjects with relapsed/refractory solid tumors. CTX131 is an is allogeneic CD70- 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-CD70 Allogeneic CRISPR-Cas9-Engineered T Cells (CTX131) in Adult Subjects With Relapsed or Refractory Solid Tumors

Conditions
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Clear Cell Renal Cell Carcinoma, Cervical Carcinoma, Esophageal Carcinoma, Pancreatic Adenocarcinoma, Malignant Pleural Mesothelioma

Intervention / Treatment
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* Biological: CTX131


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Age ≥18 years. Unresectable or metastatic, relapsed/refractory, clear cell renal cell carcinoma, cervical carcinoma, pancreatic adenocarcinoma, endometrial carcinoma, and malignant pleural mesothelioma. 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 CTX131 infusion. Key Exclusion Criteria: Prior treatment with anti-CD70 targeting agents History of certain central nervous system (CNS), cardiac or pulmonary conditions. Presence of uncontrolled bacterial, viral, or fungal infection. Active HIV, hepatitis B virus or hepatitis C virus infection. 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: CTX131<br>Administered by IV infusion following lymphodepleting chemotherapy. | Biological: CTX131<br>* CTX131 (CD70-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 CTX131 infusion up to 28 days post-infusion | 
| Phase 2 (Cohort Expansion): Objective response rate (ORR) | ORR based on Independent Review Committee (IRC) assessment, defined as the proportion of subjects who have achieved a best overall response of CR or PR according to appropriate response evaluation criteria for each disease histology | From CTX131 infusion up to 60 months post-infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAR-T, Allogeneic, Carcinoma