DNA Plasmid-encoding Interleukin-12/HPV DNA Plasmids Therapeutic Vaccine INO-3112 and Durvalumab in Treating Patients With Recurrent or Metastatic Human Papillomavirus Associated Cancers

Recurrent Cervical Carcinoma Clinical Trial

Official title: A Phase 2, Open-Label Study to Evaluate Efficacy of Combination Treatment With MEDI0457 (INO-3112) and Durvalumab (MEDI4736) in Patients With Recurrent/Metastatic Human Papilloma Virus Associated Cancers

Status Active, not recruiting

Clinical Trial Summary

This phase II trial studies how well deoxyribonucleic acid (DNA) plasmid-encoding interleukin-12/human papillomavirus (HPV) DNA plasmids therapeutic vaccine INO-3112 and durvalumab work in treating patients with human papillomavirus associated cancers that have come back or spread to other places in the body. Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving DNA plasmid-encoding interleukin-12/HPV DNA plasmids therapeutic vaccine INO-3112 and durvalumab may work better in treating patients with human papillomavirus associated cancers.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To evaluate the anti-tumor activity of DNA plasmid-encoding interleukin-12/HPV DNA plasmids therapeutic vaccine INO-3112 (MEDI0457) in combination with durvalumab.

SECONDARY OBJECTIVES:

I. To determine the safety profile of MEDI0457 in combination with durvalumab in patients with recurrent/metastatic human papilloma virus (HPV) 16- or 18- associated cancer.

II. To evaluate the progression-free survival (PFS) and overall survival (OS) of patients with recurrent/metastatic incurable HPV-16/18 positive solid malignancies receiving the combination of MEDI0457and durvalumab.

III. To evaluate objective response rate (ORR) by immune-related criteria of the combination of MEDI0457 and durvalumab in patients with recurrent/metastatic incurable HPV-16/18 positive solid malignancies.

IV. To evaluate the disease control rate at 24 weeks.

EXPLORATORY OBJECTIVES:

I. To determine the cellular and humoral immune response to immunotherapy with MEDI0457 in combination with durvalumab,

II. To examine the correlation between anti tumor activity and biomarkers including:

IIa. HPV-specific cellular and humoral responses. IIb. Programmed death ligand 1 status. IIc. The number of tumor infiltrating lymphocytes, HPV 16/18 E6/E7 deoxyribonucleic acid (DNA) levels and HPV 16/18 E6/E7 DNA sequence in biopsy tissue and plasma.

III. To evaluate the pharmacokinetics and anti-drug antibodies (ADA) for durvalumab.

OUTLINE:

Patients receive DNA plasmid-encoding interleukin-12/HPV DNA plasmids therapeutic vaccine INO-3112 intramuscularly (IM) and via electroporation at 1, 3, 7, and 12 weeks and durvalumab intravenously (IV) at 4, 8, and 12 weeks. Starting week 12, cycles repeat every 8 weeks for DNA plasmid-encoding interleukin-12/HPV DNA plasmids therapeutic vaccine INO-3112 and every 4 weeks for up to 13 doses of durvalumab in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 90 days, every 3 months for 12 months, and then every 6 months thereafter. ;

Related Conditions & MeSH terms

• Anus Neoplasms
• Carcinoma
• Human Papillomavirus-16 Positive
• Human Papillomavirus-18 Positive
• Metastatic Malignant Neoplasm
• Neoplasms
• Penile Neoplasms
• Recurrence
• Recurrent Anal Canal Carcinoma
• Recurrent Cervical Carcinoma
• Recurrent Malignant Neoplasm
• Recurrent Penile Carcinoma
• Recurrent Vaginal Carcinoma
• Recurrent Vulvar Carcinoma
• Refractory Malignant Neoplasm
• Stage IV Anal Cancer AJCC v8
• Stage IV Cervical Cancer AJCC v8
• Stage IV Penile Cancer AJCC v8
• Stage IV Vaginal Cancer AJCC v8
• Stage IV Vulvar Cancer AJCC v8
• Stage IVA Cervical Cancer AJCC v8
• Stage IVA Vaginal Cancer AJCC v8
• Stage IVA Vulvar Cancer AJCC v8
• Stage IVB Cervical Cancer AJCC v8
• Stage IVB Vaginal Cancer AJCC v8
• Stage IVB Vulvar Cancer AJCC v8
• Uterine Cervical Neoplasms
• Vaginal Neoplasms
• Vulvar Neoplasms

• NCT number: NCT03439085
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 14, 2018
• Completion date: December 31, 2022