Single Patient Protocol: A Phase II Study Using the Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Mutated Neoantigens in a Patient With Metastatic Cancer Plus the Administration of Pembrolizumab

Study Overview
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Brief Summary
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Single Patient Expanded Access

Detailed Description
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Background: Please refer to National Cancer Institute Surgery Branch (NCI-SB) protocol 18-C-0049, Amendment F. Objective: Under Individual Patient Expanded Access, to treat a patient with metastatic prostate cancer with autologous peripheral blood lymphocytes (PBL) that have been transduced with genes encoding T-cell receptors that recognize the mutated TP53 shared oncogene in the autologous cancer. Eligibility: Must have measurable, metastatic disease as assessed per RECIST v1.1 criteria. Must sign the informed consent document. Willing to sign Durable Power of Attorney Form. Must have all regulatory approvals prior to start of treatment. Design: Please refer to NCI-SB protocol 18-C-0049, Amendment F. The patient will be treated with a non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine, followed by the infusion of autologous transduced PBL and then high-dose aldesleukin. The patient will also receive pembrolizumab on Day -2 prior to cell administration and additional doses every 3 weeks following cell infusion until the time of disease progression.

Official Title
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Single Patient Protocol: A Phase II Study Using the Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Mutated Neoantigens in a Patient With Metastatic Cancer Plus the Administration of Pembrolizumab

Intervention / Treatment
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* Biological: Individual Patient TCR Transduced PBL
* Drug: Cyclophosphamide
* Drug: Fludarabine
* Drug: Aldesleukin
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Measurable (per RECIST v1.1 criteria), metastatic prostate cancer. Refractory to approved standard systemic therapy. Ability of subject to understand and the willingness to sign a written informed consent document. Willing to sign a Durable Power of Attorney Form. Willing to practice birth control from the time of enrollment on this study and for four months after treatment. Subject must be co-enrolled on protocol 03-C-0277. Exclusion Criteria: Not applicable.

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: Individual Patient TCR Transduced PBL|Day 0: Cells will be infused at a dose not to exceed .5e11 in 400 mL IV on the Patient Care Unit over 20-30 minutes (2-4 days after the last dose of fludarabine).|
|Drug: Cyclophosphamide|Days -7 and -6: Cyclophosphamide 60 mg/kg/day x 2 days IV in 250 mL D5W infused simultaneously with mesna 15 mg/kg/day over 1 hour x 2 days.|
|Drug: Fludarabine|Days -7 to -3: Fludarabine 25 mg/m2 /day IVPB daily over 30 minutes for 5 days.|
|Drug: Aldesleukin|Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 10 doses).|
|Drug: Pembrolizumab|Pembrolizumab 2 mg /kg IV over approximately 30 minutes on Day -2 and then every 3 weeks until time of disease progression.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |