Safety and Efficacy of ALLO-316 in Subjects With Advanced or Metastatic Clear Cell Renal Cell Carcinoma

Study Overview
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Brief Summary
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This is a Phase 1 dose escalation study following a 3+3 study design. The purpose of the TRAVERSE study is to assess the safety, efficacy, and cell kinetics of ALLO-316 in adults with advanced or metastatic clear cell renal cell carcinoma after a lymphodepletion regimen comprising fludarabine, cyclophosphamide, and ALLO-647 to define a Phase 2 dose.

Official Title
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A Phase 1 Multicenter Study Evaluating the Safety and Efficacy of ALLO-316 Following ALLO-647 Containing Conditioning Regimen in Subjects With Advanced or Metastatic Clear Cell Renal Cell Carcinoma

Conditions
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Advanced/Metastatic Clear Cell Renal Cell Carcinoma

Intervention / Treatment
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* Genetic: ALLO-316
* Biological: ALLO-647
* Drug: Fludarabine
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed renal cell carcinoma with a predominant clear cell component. Must have received a checkpoint inhibitor and a VEGF inhibitor in the advanced and/or metastatic setting. At least one measurable lesion as defined by RECIST version 1.1 Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1. Absence of donor (product)-specific anti-HLA antibodies (DSA). Adequate hematological, renal, liver, pulmonary, and cardiac functions. Exclusion Criteria: Central nervous system (CNS) metastatic disease (unless controlled and stable for at least 4 weeks), leptomeningeal disease, or cord compression. Clinically significant CNS dysfunction. Any other active malignancy within 3 years prior to enrollment. Prior treatment with anti-CD70 therapies. Current thyroid disorder (including hyperthyroidism) with the exception of hypothyroidism controlled on stable dose of hormone replacement therapy. Prior treatment with anti-CD52 monoclonal antibody in the past 12 months. Patients unwilling to participate in the extended safety monitoring period.

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: ALLO-647, ALLO-316<br> | Genetic: ALLO-316<br>* ALLO-316 is an allogeneic CAR T cell therapy targeting CD70<br>Biological: ALLO-647<br>* ALLO-647 is a monoclonal antibody that recognizes a CD52 antigen<br>Drug: Fludarabine<br>* Chemotherapy for lymphodepletion<br>Drug: Cyclophosphamide<br>* Chemotherapy for lymphodepletion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects experiencing Dose Limiting Toxicities at increasing doses of ALLO-316 |  | 28 days | 
| Proportion of patients experiencing Dose Limiting Toxicity with ALLO-647 in combination with fludarabine/cyclophosphamide administered prior to ALLO-316 |  | 33 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAR T, Cell Therapy, Allogeneic Cell Therapy, Cellular Immuno-therapy, AlloCAR T, ALLO-316, ALLO-647, CCRCC, Clear Cell Renal Cell Carcinoma