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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 : June 12, 2019
Sponsor:
Information provided by (Responsible Party):
Inovio Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE April 11, 2018
First Posted Date  ICMJE April 19, 2018
Last Update Posted Date June 12, 2019
Actual Study Start Date  ICMJE May 24, 2018
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 11, 2018)
  • 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) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03502785 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 11, 2018)
  • 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) ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE INO-5401 + INO-9012 in Combination With Atezolizumab in Locally Advanced Unresectable or Metastatic/Recurrent Urothelial Carcinoma
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Urothelial Carcinoma
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • 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.
    Interventions:
    • Biological: INO-5401
    • Biological: INO-9012
    • Drug: Atezolizumab
    • Device: CELLECTRA™ 2000
  • 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.
    Interventions:
    • Biological: INO-5401
    • Biological: INO-9012
    • Drug: Atezolizumab
    • Device: CELLECTRA™ 2000
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 11, 2018)
85
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2020
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Inovio Call Center 267-440-4237 clinical.trials@inovio.com
Listed Location Countries  ICMJE Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03502785
Other Study ID Numbers  ICMJE UCa-001
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Inovio Pharmaceuticals
Study Sponsor  ICMJE Inovio Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Jeffrey Skolnik, MD Inovio Pharmaceuticals
PRS Account Inovio Pharmaceuticals
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP