Clinical Trials /

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

NCT03502785

Description:

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.

Related Conditions:
  • Urothelial Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: UCa-001
  • NCT ID: NCT03502785

Conditions

  • Urothelial Carcinoma

Interventions

DrugSynonymsArms
INO-5401Cohort A
INO-9012Cohort A
AtezolizumabCohort A

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Cohort AExperimentalParticipants 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.
  • INO-5401
  • INO-9012
  • Atezolizumab
Cohort BExperimentalParticipants 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.
  • INO-5401
  • INO-9012
  • Atezolizumab

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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)
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description:
Measure:ORR by Immune RECIST (iRECIST)
Time Frame:From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years)
Safety Issue:
Description:
Measure:Duration of Response (DoR)
Time Frame:From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:: From Baseline to the time of death from any cause (up to approximately 2 years)
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Inovio Pharmaceuticals

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