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

NCT03502785 | Completed Phase 1 Results FDA Drug FDA Device

• 1 other identifier: UCa-001
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 11

Brief Summary

This was 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 was divided into two cohorts: Cohort A: participants with locally advanced unresectable or metastatic/recurrent UCa, who had 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 were treatment naïve and ineligible for cisplatin-based chemotherapy. A safety run-in was performed using a modified rolling six design, enrolling up to 6 participants (safety analysis participants) from Cohort A.

Conditions

Urothelial Carcinoma

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Adverse Events of Special Interest (AESIs) Treatment

  An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. TEAEs were defined as any AEs that occurred on or after Day 0. AESIs were toxicities and immune-mediated AEs that may have occurred up to 90 days after the last dose of trial treatment. AESIs were reported by the investigator to the Sponsor within 24 hours after learning of the event.

  Up to approximately 71 months

• Number of Participants With Clinically Significant Changes in Hematological Parameters

  Clinically significant changes in hematological parameters were determined based on the investigator's discretion.

  Up to approximately 71 months

• Number of Participants With Clinically Significant Changes in Serum Chemistry Parameters

  Clinically significant changes in serum chemistry parameters were determined based on the investigator's discretion.

  Up to approximately 71 months

• Number of Participants With Clinically Significant Changes in Urinalysis Parameters

  Clinically significant changes in urinalysis parameters were determined based on the investigator's discretion.

  At baseline, Weeks 3, 6, 9, then every 6 weeks thereafter, up to 71 months

• Antigen-Specific Immune Response

  Blood and tissue samples were collected to evaluate the antigen-specific immune response to INO-5401 + INO-9012 in combination with atezolizumab. Planned assessments included: Enzyme Linked Immunosorbent Spot-forming (ELISpot) Assay, Flow cytometry, T cell receptor (TCR) sequencing, ELISA and/or gene expression analysis.

  Up to approximately 71 months

• Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Review in Cohort A

  ORR was defined as the percentage of participants who had a confirmed complete response (CR) or a partial response (PR). CR was defined as disappearance of all target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters) per RECIST 1.1.

  From date of treatment start until date of first PD or death (whichever occurred first), up to approximately 71 months

Secondary Outcomes (6)

• ORR as Assessed by RECIST Version 1.1 by Investigator Review in Cohort B

  From date of treatment start until date of first PD or death (whichever occurred first), up to approximately 71 months

• Percentage of Participants With ORR by Immune Response Evaluation Criteria in Solid Tumors (iRECIST)

  From date of treatment start until date of first PD or death (whichever occurred first), up to approximately 71 months

• Duration of Response (DoR)

  From first documented confirmed CR or PR until first documentation of PD or death, whichever occurred first (approximately 71 months)

• Progression-Free Survival (PFS) Per RECIST Version 1.1

  From the first dose of study drug to date of PD or death, whichever occurred first (up to approximately 71 months)

• PFS Per Immune RECIST (iRECIST)

  From Baseline to disease progression or death, whichever occurs first (up to approximately 71 months)

Study Arms (2)

Cohort A: Prior Anti-PD-1/PD-L1

EXPERIMENTAL

Participants with locally advanced unresectable or metastatic/recurrent UCa, who had confirmed disease progression during or following treatment with anti- programmed death receptor-1/ programmed cell death-ligand 1 (PD-1/PD-L1) therapy received INO-5401 9 milligrams (mg) and INO-9012 1 mg, intramuscular (IM) injection, followed by electroporation (EP) by CELLECTRA® 2000 device, every 3 weeks until Week 9, then every 6 weeks for 6 more doses (until Week 45), thereafter every 12 weeks, until confirmed disease progression, unacceptable toxicity, or deemed intolerable by the investigator in combination with atezolizumab 1200 mg, intravenous (IV) infusion, every 3 weeks, until confirmed disease progression, unacceptable toxicity, or deemed intolerable by the investigator.

Biological: INO-5401; Biological: INO-9012; Drug: Atezolizumab; Device: CELLECTRA® 2000

Cohort B: Naïve Anti-PD-1/PD-L1

EXPERIMENTAL

Participants with locally advanced unresectable or metastatic/recurrent UCa who are treatment naïve and ineligible for cisplatin-based chemotherapy received INO-5401 9 mg and INO-9012 1 mg, IM injection, followed by EP by CELLECTRA® 2000 device, every 3 weeks until Week 9, then every 6 weeks for 6 more doses (until Week 45), thereafter every 12 weeks, until confirmed disease progression, unacceptable toxicity, or deemed intolerable by the investigator in combination with atezolizumab 1200 mg, IV infusion, every 3 weeks, until confirmed disease progression, unacceptable toxicity, or deemed intolerable by the investigator.

Biological: INO-5401; Biological: INO-9012; Drug: Atezolizumab; Device: CELLECTRA® 2000

Interventions

INO-9012 BIOLOGICAL

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

Cohort A: Prior Anti-PD-1/PD-L1; Cohort B: Naïve Anti-PD-1/PD-L1

Atezolizumab DRUG

IV-Infusion.

Cohort A: Prior Anti-PD-1/PD-L1; Cohort B: Naïve Anti-PD-1/PD-L1

CELLECTRA® 2000 DEVICE

IM injection.

Cohort A: Prior Anti-PD-1/PD-L1; Cohort B: Naïve Anti-PD-1/PD-L1

INO-5401 BIOLOGICAL

INO-5401: A 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. IM injection

Cohort A: Prior Anti-PD-1/PD-L1; Cohort B: Naïve Anti-PD-1/PD-L1

Eligibility Criteria

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

You may qualify if:

• 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: Participants 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 Response Evaluation Criteria in Solid Tumors (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 participants: 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.

You may not qualify if:

• 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 participant'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 participant to participate in the opinion of the treating investigator;

Sponsors & Collaborators

• Inovio Pharmaceuticals: lead

Study Sites (11)

Mayo Clinic Cancer Center

Phoenix, Arizona, 85054, United States

Location

H. Lee Moffitt Cancer Center & Research Institute, Inc.

Tampa, Florida, 33612, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Washington University School of Medicine in St. Louis

St Louis, Missouri, 63110, United States

Location

New York University Langone Medical Center - Perlmutter Cancer Center

New York, New York, 10016, United States

Location

Columbia University, Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

University of North Carolina School of Medicine

Chapel Hill, North Carolina, 27599, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Greenville Memorial Hospital

Greenville, South Carolina, 29615, United States

Location

Inova Melanoma and Skin Cancer Center

Fairfax, Virginia, 22031, United States

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

rocakinogene sifuplasmid; atezolizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Results Point of Contact

• Title: Jeffrey Skolnik
• Organization: Inovio Pharmaceuticals

clinical.trials@inovio.com

267-440-4200

Study Officials

• Jeffrey Skolnik, MD

  Inovio Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2018
• First Posted: April 19, 2018
• Study Start: July 24, 2018
• Primary Completion: May 9, 2025
• Study Completion: May 9, 2025
• Last Updated: September 2, 2026
• Results First Posted: September 2, 2026

Record last verified: 2026-09

Locations

US (11)