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INO-5401 + INO-9012 in Combination With Atezolizumab in Locally Advanced Unresectable or Metastatic/Recurrent Urothelial Carcinoma

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ClinicalTrials.gov Identifier: NCT03502785
Recruitment Status : Recruiting
First Posted : April 19, 2018
Last Update Posted : November 28, 2018
Sponsor:
Information provided by (Responsible Party):
Inovio Pharmaceuticals

Brief Summary:
This is a Phase I/IIA, open-label, multi-center trial to evaluate the safety, immunogenicity and preliminary clinical efficacy of INO-5401 + INO-9012 delivered by intramuscular (IM) injection followed by electroporation (EP), in combination with atezolizumab in participants with locally advanced unresectable or metastatic/recurrent Urothelial Carcinoma (UCa). The trial population is divided into two cohorts: Cohort A: Participants with locally advanced unresectable or metastatic/recurrent UCa, who have confirmed disease progression during or following treatment with anti-Programmed Death receptor-1/Programmed Death receptor Ligand-1 (anti-PD-1/PD-L1) therapy; Cohort B: Participants with locally advanced unresectable or metastatic/recurrent UCa, who are treatment naïve and ineligible for cisplatin-based chemotherapy. A safety run-in will be performed with up to six participants (safety analysis participants) from cohort A.

Condition or disease Intervention/treatment Phase
Urothelial Carcinoma Biological: INO-5401 Biological: INO-9012 Drug: Atezolizumab Device: CELLECTRA® 2000 Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 85 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Multi-Center Trial of INO-5401 + INO-9012 in Combination With Atezolizumab in Subjects With Locally Advanced Unresectable or Metastatic/Recurrent Urothelial Carcinoma
Actual Study Start Date : May 24, 2018
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort A
Participants with locally advanced unresectable or metastatic/recurrent UCa, who have confirmed disease progression during or following treatment with an anti-PD-1/PD-L1 therapy. Cohort A participants will be treated with INO-5401 and INO-9012 in combination with atezolizumab.
Biological: INO-5401
INO-5401 (9 milligram [mg] dose IM): mixture of 3 synthetic plasmids that target Wilms' tumor gene-1 (WT1) antigen, prostate-specific membrane antigen (PSMA) and human telomerase reverse transcriptase (hTERT) antigen.

Biological: INO-9012

INO-9012 (1 mg dose IM): A synthetic plasmid that expresses human interleukin-12 (IL-12).

INO-5401 + INO-9012 will be administered IM followed by EP with CELLECTRA® 2000 device every 3 weeks for 4 doses then every 6 weeks for 6 additional doses, thereafter every 12 weeks until confirmed disease progression, unacceptable toxicity, or deemed intolerable by the investigator.


Drug: Atezolizumab
Atezolizumab will be administered by intravenous (IV) infusion every 3 weeks until confirmed disease progression, unacceptable toxicity, or deemed intolerable by the investigator.

Device: CELLECTRA® 2000
IM injection of INO-5401 and INO-9012 is followed by EP with the CELLECTRA® 2000 device.

Experimental: Cohort B
Participants with locally advanced unresectable or metastatic/recurrent UCa who are treatment naïve and ineligible for cisplatin-based chemotherapy. Cohort B participants will be treated with INO-5401 and INO-9012 in combination with atezolizumab.
Biological: INO-5401
INO-5401 (9 milligram [mg] dose IM): mixture of 3 synthetic plasmids that target Wilms' tumor gene-1 (WT1) antigen, prostate-specific membrane antigen (PSMA) and human telomerase reverse transcriptase (hTERT) antigen.

Biological: INO-9012

INO-9012 (1 mg dose IM): A synthetic plasmid that expresses human interleukin-12 (IL-12).

INO-5401 + INO-9012 will be administered IM followed by EP with CELLECTRA® 2000 device every 3 weeks for 4 doses then every 6 weeks for 6 additional doses, thereafter every 12 weeks until confirmed disease progression, unacceptable toxicity, or deemed intolerable by the investigator.


Drug: Atezolizumab
Atezolizumab will be administered by intravenous (IV) infusion every 3 weeks until confirmed disease progression, unacceptable toxicity, or deemed intolerable by the investigator.

Device: CELLECTRA® 2000
IM injection of INO-5401 and INO-9012 is followed by EP with the CELLECTRA® 2000 device.




Primary Outcome Measures :
  1. Number of Adverse Events [ Time Frame: From baseline up to 90 days after last dose of study medication (up to approximately 2 years and 3 months) ]
  2. Antigen-Specific Cellular Immune Response [ Time Frame: At baseline, Weeks 3, 6, 9, 12 and every 12 weeks thereafter up to end of study (up to approximately 2 years) ]
  3. Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator Review in Cohort A [ Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years) ]

Secondary Outcome Measures :
  1. ORR by RECIST version 1.1 by Investigator Review in Cohort B [ Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years) ]
  2. ORR by Immune RECIST (iRECIST) [ Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years) ]
  3. Duration of Response (DoR) [ Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years) ]
  4. Progression Free Survival (PFS) as Assessed by RECIST version 1.1 and iRECIST [ Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years) ]
  5. Overall Survival (OS) [ Time Frame: : From Baseline to the time of death from any cause (up to approximately 2 years) ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Sign an Informed Consent Form (ICF);
  • Have histologically or cytologically documented locally advanced unresectable or metastatic/recurrent urothelial carcinoma (including renal pelvis, ureters, urinary bladder, and urethra);
  • For Cohort A: Subjects who have radiographically confirmed disease progression during or following treatment with an anti-PD-1/PD-L1 based therapy;
  • For Cohort B: No prior chemotherapy for inoperable locally advanced or metastatic or recurrent UCa and ineligible ("unfit") for cisplatin-based chemotherapy;
  • Have measurable disease, as defined by RECIST version 1.1;
  • Have a performance status of 0 or 1 on Eastern Cooperative Oncology Group (ECOG) Performance Scale;
  • Have life expectancy of >/= 3 months;
  • Be willing to provide a tissue sample for pre-treatment intra-tumoral assessment of proinflammatory and immunosuppressive factors;
  • Have electrocardiogram (ECG) with no clinically significant findings as assessed by the investigator performed within 28 days prior to first dose;
  • Demonstrate adequate hematological, renal, hepatic, and coagulation function;
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 5 months after the last dose of study treatment;
  • For male subjects: agreement not to father a child. Participants must be surgically sterile (e.g, vasectomy) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 5 months after the last dose of study treatment.

Exclusion Criteria:

  • Any approved anti-cancer therapy including chemotherapy, targeted small molecule therapy or radiation therapy within 2 weeks prior to trial Day 0 as well as current participation or recipient of treatment on a clinical trial within 28 days prior to Day 0;
  • Documented active or untreated central nervous system (CNS) metastases and/or carcinomatous meningitis;
  • Malignancies other than UCa within 3 years prior to Day 0, with the exception of those with negligible risk of metastasis or death treated with expected curative outcome;
  • Prior treatment with CD137 agonists or immune checkpoint blockade therapies;
  • Treatment with systemic immunostimulatory agents;
  • Treatment with systemic immunosuppressive medication;
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins;
  • Known hypersensitivity allergy or contraindication to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the PD-1/PD-L1 inhibitor formulation;
  • Active or history of autoimmune disease or immune deficiency;
  • History or any evidence of interstitial lung disease;
  • History of human immunodeficiency virus (HIV);
  • Active hepatitis B or active hepatitis C;
  • Severe infections within 4 weeks prior to enrollment;
  • Received therapeutic oral or IV antibiotics within 2 weeks prior to Day 0;
  • History or current evidence of any condition, therapy or laboratory abnormality that might confound the results of the trial; interfere with the subject's participation for the full duration of the trial, or is negatively impacted by EP treatment, or is not in the best interest of the subject to participate in the opinion of the treating investigator;
  • Prior allogeneic stem cell or solid organ transplant;
  • Uncontrolled tumor-related pain; pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures; or, hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03502785


Contacts
Contact: Inovio Call Center 267-440-4237 clinical.trials@inovio.com

Locations
United States, Alaska
Alaska Clinical Research Center, LLC Recruiting
Anchorage, Alaska, United States, 99503
Contact: Study Coordinator Talia Wyckoff    907-276-1455    TWyckoff@akmed.com   
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute, Inc. Recruiting
Tampa, Florida, United States, 33612
Contact: Study Coordinator Yazmin Rodriguez    813-745-3353    Yazmin.Rodriguez@moffitt.org   
United States, Indiana
Indiana University Simon Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Clinical Research Nurse Christin Snow, RN, BSN    317-274-5830    chsnow@iu.edu   
United States, Michigan
Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Study Coordinator Veena Ramakrishna    313-576-9703    ramakriv@karmanos.org   
United States, Missouri
Washington University School of Medicine in St. Louis Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Study Coordinator Andrew Atkocius    314-747-1343    a.atkocius@wustl.edu   
United States, New York
Columbia University, Herbert Irving Comprehensive Cancer Center Recruiting
New York, New York, United States, 10032
Contact: Study Coordinator Bridget James    212-304-5543    bb2771@cumc.columbia.edu   
United States, Pennsylvania
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Study Coordinator Daniel Mocan, RN    412-235-1319    mocand@upmc.edu   
United States, South Carolina
Greenville Memorial Hospital Recruiting
Greenville, South Carolina, United States, 29615
Contact: Study Coordinator Gina Norris    864-241-6251    gnorris@ghs.org   
Spain
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain, 28041
Contact: Principal Investigator Daniel Castellano       dcastellano.ec@gmail.com   
Sponsors and Collaborators
Inovio Pharmaceuticals
Investigators
Study Director: Jeffrey Skolnik, MD Inovio Pharmaceuticals

Responsible Party: Inovio Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03502785     History of Changes
Other Study ID Numbers: UCa-001
First Posted: April 19, 2018    Key Record Dates
Last Update Posted: November 28, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Pediatric Postmarket Surveillance of a Device Product: No

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Atezolizumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs