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

NCT03439085 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 2017-0302NCI-2018-00914
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Human Papillomavirus-16 Positive; Human Papillomavirus-18 Positive; Metastatic Malignant Neoplasm; 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

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  Will be evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Will be estimated with 95% confidence interval.

  Up to 2 years

Secondary Outcomes (3)

• Disease Control Rate

  Up to 2 years

• Median Progression Free Survival (PFS)

  Up to 2 years

• Median Overall Survival

  Up to 2 years

Study Arms (1)

Treatment (INO-3112, durvalumab)

EXPERIMENTAL

Patients receive DNA plasmid-encoding interleukin-12/HPV DNA plasmids therapeutic vaccine INO-3112 IM and via electroporation at 1, 3, 7, and 12 weeks and durvalumab 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.

Biological: DNA Plasmid-encoding Interleukin-12/HPV DNA Plasmids Therapeutic Vaccine MEDI0457; Biological: Durvalumab

Interventions

DNA Plasmid-encoding Interleukin-12/HPV DNA Plasmids Therapeutic Vaccine MEDI0457 BIOLOGICAL

Given IM and via electroporation

Also known as: INO 3112, INO-3112, INO-3112 Vaccine, MEDI 0457, MEDI-0457, MEDI0457, VGX-3100 Plus INO-9012

Treatment (INO-3112, durvalumab)

Durvalumab BIOLOGICAL

Given IV

Also known as: Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736

Treatment (INO-3112, durvalumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent in accordance with institutional guidelines.
• Are able and willing to comply with all study procedures.
• For patients who are not human immunodeficiency virus (HIV) positive, cervical, anal, penile, vulvar, or vaginal cancer positive for HPV-16 and/or HPV-18 by the institutionally approved assay. For patients who are HIV positive, histologically or cytologically confirmed diagnosis of cancer at any site that is positive for HPV-16 and/or HPV-18 by the institutionally approved assay. Tumors may be positive for more than 1 HPV subtype as long as HPV-16 and/or HPV-18 is present. Note: For the first 3 patients, only cervical, vulvar, or vaginal cancers will be enrolled.
• Patients with cancer that is refractory to standard therapy, that have either relapsed after standard therapy or has no standard therapy that increases survival by at least three months, and/or that are not curable by salvage approaches including resection and/or re-irradiation
• Has measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) with a minimum size of 10 mm by computed tomography (CT) scan, except lymph nodes which must have minimum short axis size of 15 mm (CT scan slice thickness no greater than 5 mm in both cases). Indicator lesions must not have been previously treated with surgery, radiation therapy, or radiofrequency ablation unless there is documented Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 progression in the lesion after such therapy.
• All patients must consent to pre-treatment biopsy of the tumor if it can be done safely (as judged by the investigator) during screening. Week 10 on-treatment biopsies will be required for a minimum 10 patients. After 10 paired biopsies have been obtained then week 10 on-treatment biopsy will be made optional.
• World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Hemoglobin \>= 9 g/dL (Note: Note: No Transfusion within 7 days of beginning study treatment. Ongoing growth factor support is acceptable if on a stable dose for the past 56 days), within 28 days of day 0.
• Cannot be met with recent blood transfusions or require ongoing growth factor support
• Absolute neutrophil count \>= 1,000/mm\^3, within 28 days of day 0.
• Cannot be met with recent blood transfusions or require ongoing growth factor support
• Platelet count \>= 100,000/mm\^3 and no transfusion in prior 4 weeks, within 28 days of day 0.
• Cannot be met with recent blood transfusions or require ongoing growth factor support
• Total bilirubin (TBL) =\< 1.5 x upper limit of normal (ULN) except patients with documented Gilbert's syndrome (\> 3 x ULN), within 28 days of day 0.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x ULN, within 28 days of day 0.

You may not qualify if:

• Any concurrent chemotherapy, investigational product (IP), biologic, or hormonal therapy for cancer treatment; receipt of any investigational or approved anticancer therapy (chemotherapy, targeted therapy, biologic therapy, monoclonal antibodies, etc.) within 21 days or 5 half lives, whichever is shorter, prior to the first dose of MEDI0457; concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• Major surgical procedure or significant traumatic injury within 28 days before the first dose of study drug or anticipation of the need for major surgery during the course of study treatment.
• Current or prior use of immunosuppressive medication within 14 days prior to first study dose, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent. Steroids as premedication for hypersensitivity reactions due to radiographic contrast agents are allowed.
• Patients requiring therapeutic anticoagulation and irreversible platelet inhibitors (e.g. clopidogrel, prasugrel, or ticagrelor). Low dose aspirin for cardiac prophylaxis is allowed.
• History of primary immunodeficiency.
• Patients who have had prior exposure to immune-mediated therapy, including but not limited to prior exposure to T-cell and natural killer cell directed therapy, anti-PD-1, anti-PD-L1, anti-CD137, and anti-CTLA4.
• History of allogeneic organ transplantation.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g. colitis, ulcerative colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions to this criterion: patients with vitiligo or alopecia, patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement, any chronic skin condition that does not require systemic therapy, patients without active disease in the last 5 years may be included but only after consultation with the study physician, and patients with celiac disease controlled by diet alone.
• Uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, uncontrolled hypertension, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events, or compromise the ability of the patient to give written informed consent.
• Patients with spinal cord compression or a history of leptomeningeal carcinomatosis. At the time of day 1 of the study, patients with central nervous system metastases must have been treated and must be asymptomatic and meet the following criteria. 1. No concurrent treatment, inclusive of, but not limited to, surgery, radiation, and/or corticosteroids. (Note: patients are allowed on systemic steroids unless these are being administered to manage central nervous system metastases); 2. Neurologic stability (lack of signs or symptoms greater than baseline prior to radiotherapy) until the time of dosing of MEDI0457; 3. For radiation treatment, patients must be: at least 14 days between last day of stereotactic radiosurgery or gamma-knife treatment and day 1 of protocol treatment, at least 28 days between last day of whole brain radiation therapy and day 1 of protocol treatment, and/or at least 14 days since last dose of corticosteroids and day 1 of protocol treatment.
• Patients with cardiovascular (CV) disease conditions including New York Heart Association class 3 or 4 congestive heart failure, unstable angina pectoris, or clinically important cardiac arrhythmias OR a recent (\< 3 months) CV event, including myocardial infarction, unstable angina pectoris, or stroke.
• Mean QT interval corrected for heart rate (QTc) \>= 470 ms calculated from electrocardiogram (ECG) using Fridericia's correction by manual read.
• Active tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice) infection.
• Presence of acute or chronic hepatitis B (hepatitis B virus \[HBV\]) or active hepatitis C (hepatitis C virus \[HCV\]). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBV surface antigen \[HBsAg\]) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA).
• Receipt of live, attenuated vaccine within 30 days prior to study entry or the first dose of MEDI0457.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Neoplasm Metastasis; Anal Canal Carcinoma; Uterine Cervical Neoplasms; Recurrence; Penile Neoplasms; Vaginal Neoplasms; Vulvar Neoplasms; Neoplasms; Anus Neoplasms

Interventions

MEDI0457; VGX-3100; rocakinogene sifuplasmid; durvalumab; Immunoglobulin G; Disulfides

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Disease Attributes; Genital Neoplasms, Male; Genital Diseases, Male; Penile Diseases; Male Urogenital Diseases; Vaginal Diseases; Vulvar Diseases; Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Results Point of Contact

• Title: Dr. Michael Frumovitz, Chief Patient Experience Ofc, Ofc of Chief Operating Officer
• Organization: UT MD Anderson Cancer Center

mfrumovitz@mdanderson.org

(713) 792-9599

Study Officials

• Michael M Frumovitz

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2018
• First Posted: February 20, 2018
• Study Start: November 14, 2018
• Primary Completion: September 20, 2022
• Study Completion: September 20, 2022
• Last Updated: July 9, 2024
• Results First Posted: July 9, 2024

Record last verified: 2024-05

Locations

US (1)