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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
35
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.
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.
Atezolizumab will be administered by intravenous (IV) infusion every 3 weeks until confirmed disease progression, unacceptable toxicity, or deemed intolerable by the investigator.
IM injection of INO-5401 and INO-9012 is followed by EP with the CELLECTRA™ 2000 device.
Mayo Clinic Cancer Center
Phoenix, Arizona, United States
H. Lee Moffitt Cancer Center & Research Institute, Inc.
Tampa, Florida, United States
Johns Hopkins University School of Medicine
Baltimore, Maryland, United States
Karmanos Cancer Institute
Detroit, Michigan, United States
Washington University School of Medicine in St. Louis
St Louis, Missouri, United States
New York University Langone Medical Center - Perlmutter Cancer Center
New York, New York, United States
Columbia University, Herbert Irving Comprehensive Cancer Center
New York, New York, United States
University of North Carolina School of Medicine
Chapel Hill, North Carolina, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States
Greenville Memorial Hospital
Greenville, South Carolina, United States
...and 1 more locations
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)
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)
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)
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)
ORR by Immune RECIST (iRECIST)
Time frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years)
Duration of Response (DoR)
Time frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years)
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)
Overall Survival (OS)
Time frame: : From Baseline to the time of death from any cause (up to approximately 2 years)
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