Optimizing Antitumor Immunity Using Plasmid Electroporation, Pembrolizumab, and Epacadostat

Recurrent Head and Neck Squamous Cell Carcinoma Clinical Trial

Official title: The Trifecta Study: Optimizing Antitumor Immunity Using Plasmid Electroporation, Pembrolizumab, and Epacadostat

Status Terminated

Clinical Trial Summary

This phase II trial studies how well tavokinogene telseplasmid with electroporation (tavo-EP), pembrolizumab, and epacadostat work in treating patients with squamous cell carcinoma of the head and neck that cannot be removed by surgery. Tavokinogene telseplasmid with electroporation is a gene therapy that may delay of tumor growth and which may have less toxicity than other methods of gene delivery. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Epacadostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving tavokinogene telseplasmid with electroporation, pembrolizumab, and epacadostat may work better in treating squamous cell carcinoma of the head and neck.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. Dose Escalation Safety Lead-Ins: Assess the safety of tavo-EP and pembrolizumab in combination with epacadostat (CTCAE version 4).

II. Dose Expansion: Determine whether the combination therapy in each arm increases the best overall response rate (BORR) compared with historical data for pembrolizumab monotherapy

SECONDARY OBJECTIVES:

I. Dose Expansion: Determine the durability of clinical benefits in participants treated with combination therapy in each arm, as assessed by time to progression, median progression-free survival (PFS), median overall survival (OS).

EXPLORATORY OBJECTIVES:

I. Determine the effects of combination therapy on treated and untreated lesions by examining paired biopsy specimens for changes in inflammatory gene expression, relative proportion of effector versus regulatory T cells, evaluation of inflammatory cytokines, T-cell activation, clonality, and other hallmarks of immune activation.

II. Explore systemic markers of immune activation by examining circulating T-cell populations for changes in the frequency and effector function of short-lived effector cells and memory T cells.

III. Explore changes in functional immune responses using Elispot and other assays.

IV. To explore biomarkers that inform scientific understanding of this therapeutic treatment through analysis of specimens retained for Future Biomedical Research.

OUTLINE:

This is a multi-center, open label, 2-stage, double-arm, clinical trial in which participants in Stage 1 will receive either tavo-EP with pembrolizumab, and epacadostat (Arm A), tavo-EP and pembrolizumab (Arm B), or CORVax, tavo-EP and pembrolizumab (Arm C). Arms B and C will only open to enrollment if the treatment is determined to be effective in Arm A.

Participants will be followed at 3-month intervals for toxicity and radiographic imaging (1) until start of a new anti-cancer treatment, (2) until 30 days after documented disease progression, (3) until death, or (4) until 36 months from the initiation of treatment on study, whichever comes first. Each subject will be followed for overall survival until death, withdrawal of consent, or at the time of study closure, whichever occurs first. ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Metastatic Head and Neck Squamous Cell Carcinoma
• Recurrent Head and Neck Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck
• Unresectable Head and Neck Squamous Cell Carcinoma

• NCT number: NCT03823131
• Study type: Interventional
• Source: University of California, San Francisco
• Status: Terminated
• Phase: Phase 2
• Start date: May 2, 2019
• Completion date: July 31, 2022