A Safety and Efficacy Study Evaluating CTX130 in Subjects With Relapsed or Refractory Renal Cell Carcinoma (COBALT-RCC)

Study Overview
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Brief Summary
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This is a single-arm, open-label, multicenter, Phase 1 study evaluating the safety and efficacy of CTX130 in subjects with relapsed or refractory renal cell carcinoma.

Detailed Description
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The study may enroll approximately 107subjects in total.

Official Title
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A Phase 1 Dose Escalation and Cohort Expansion Study of the Safety and Efficacy of Allogeneic CRISPR-Cas9-Engineered T Cells (CTX130) in Subjects With Advanced, Relapsed or Refractory Renal Cell Carcinoma With Clear Cell Differentiation

Conditions
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Renal Cell Carcinoma

Intervention / Treatment
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* Biological: CTX130


Participation Criteria
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Eligibility Criteria
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Abbreviated Inclusion Criteria: Age ≥18 years and body weight ≥42 kg. Unresectable or metastatic RCC that has exploited standard of care treatment. Karnofsky performance status (KPS) ≥80%. 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 CTX130 infusion. Abbreviated Exclusion Criteria: Prior treatment with any anti-CD70 targeting agents. Prior treatment with any CAR T cells or any other modified T or natural killer (NK) cells. History of certain central nervous system (CNS), cardiac or pulmonary conditions. Active HIV, hepatitis B virus or hepatitis C virus infection. Previous or concurrent malignancy, except treated with curative approach not requiring systemic therapy and in remission for >12 months, or any other localized malignancy with low risk of developing into metastatic disease. Primary immunodeficiency disorder or active autoimmune disease requiring steroids and/or other immunosuppressive therapy. Prior solid organ transplantation or bone marrow transplant. Pregnant or breastfeeding females.

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: CTX130<br>Administered by IV infusion following lymphodepleting chemotherapy. | Biological: CTX130<br>* CTX130 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 |
| --- | --- | --- |
| Part A (dose escalation): Incidence of adverse events | Adverse events defined as dose-limiting toxicities | From CTX130 infusion up to 28 days post-infusion | 
| Part B (cohort expansion): Objective response rate | Objective response rate per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 | From CTX130 infusion up to 60 months post-infusion] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival |  | From date of CTX130 infusion until date of disease progression or death due to any cause, assessed up to 60 months | 
| Overall Survival |  | From date of CTX130 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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Allogeneic, Renal cell carcinoma, Renal cell carcinoma with clear cell differentiation, CRISPR-Cas9, CAR T