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

Urothelial Carcinoma Clinical Trial

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03502785
• Other study ID #: UCa-001
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: May 24, 2018
• Est. completion date: December 31, 2024

Study information

• Verified date: May 2024
• Source: Inovio Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 35
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Urothelial Carcinoma

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Alaska Clinical Research Center, LLC	Anchorage	Alaska
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	University of North Carolina School of Medicine	Chapel Hill	North Carolina
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Inova Melanoma and Skin Cancer Center	Fairfax	Virginia
United States	Cancer Treatment Centers of America at Western Regional Medical Center	Goodyear	Arizona
United States	Greenville Memorial Hospital	Greenville	South Carolina
United States	Indiana University Simon Cancer Center	Indianapolis	Indiana
United States	Mayo Clinic Hospital	Jacksonville	Florida
United States	Columbia University, Herbert Irving Comprehensive Cancer Center	New York	New York
United States	New York University Langone Medical Center - Perlmutter Cancer Center	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Mayo Clinic Cancer Center	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Washington University School of Medicine in St. Louis	Saint Louis	Missouri
United States	H. Lee Moffitt Cancer Center & Research Institute, Inc.	Tampa	Florida
United States	University of Kansas Cancer Center and Medical Pavilion	Westwood	Kansas
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina
United States	Cancer Treatment Centers of America at Midwestern Regional Medical center	Zion	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Inovio Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Adverse Events		From baseline up to 90 days after last dose of study medication (up to approximately 2 years and 3 months)
Primary	Antigen-Specific Cellular Immune Response		At baseline, Weeks 3, 6, 9, 12 and every 12 weeks thereafter up to end of study (up to approximately 2 years)
Primary	Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator Review in Cohort A		From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years)
Secondary	ORR by RECIST version 1.1 by Investigator Review in Cohort B		From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years)
Secondary	ORR by Immune RECIST (iRECIST)		From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years)
Secondary	Duration of Response (DoR)		From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years)
Secondary	Progression Free Survival (PFS) as Assessed by RECIST version 1.1 and iRECIST		From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years)
Secondary	Overall Survival (OS)		: From Baseline to the time of death from any cause (up to approximately 2 years)