Locally advanced unresectable or metastatic/recurrent Urothelial Cancer MedDRA version: 20.0 Level: LLT Classification code 10077056 Term: Urothelial carcinoma recurrent System Organ Class: 100000004864
Conditions
Interventions
Product Name: INO-5401
Product Code: INO-5401
Pharmaceutical Form: Solution for injection
INN or Proposed INN: pGX1108
Current Sponsor c
Sponsors
Inovio Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provide signed IRB approved informed consent in accordance with institutional guidelines. 2. Be 18 years of age or older on the day of signing the informed consent, and able and willing to comply with all trial procedures. 3. Have histologically or cytologically documented locally advanced unresectable or metastatic/recurrent urothelial carcinoma (including renal pelvis, ureters, urinary bladder, and urethra). a) For Cohort A: Subjects who have radiographically confirmed disease progression during or following treatment with an anti-PD-1/PD-L1 based therapy. b) For Cohort B: i. No prior chemotherapy for inoperable locally advanced or metastatic or recurrent UCa - For subjects who received prior adjuvant/neoadjuvant chemotherapy or chemoradiation for UCa, a treatment-free interval greater than 12 months between the last treatment administration and the date of recurrence is required in order to be considered treatment naive in the metastatic setting. - Prior local intervesical chemotherapy or intravesical immunotherapy is allowed if completed at least 4 weeks prior to the initiation of trial treatment. ii. Ineligible (“unfit”) for cisplatin-based chemotherapy as defined by any one of the following criteria: - Impaired renal function (glomerular filtration rate [GFR] > 30 but < 60 mL/min); GFR should be assessed by direct measurement (i.e., creatinine clearance or ethyldediaminetetra-acetate) or, if not available, by calculation from serum/plasma creatinine (Cockcroft-Gault formula) - A hearing loss (measured by audiometry) of 25 dB at two contiguous frequencies - Grade 2 or greater peripheral neuropathy (i.e., sensory alteration or parasthesias including tingling) 4. Have measurable disease, as defined by RECIST version 1.1 (investigator assessment). Target lesions must not have been previously treated with surgery, radiation therapy, or radiofrequency ablation unless there is documented progression in the lesion after such therapy and no other lesions are available for selection as target lesions; 5. Have a performance status of 0 or 1 on Eastern Cooperative Oncology Group (ECOG) Performance Scale; 6. Have a life expectancy of = 3 months; 7. Be willing to provide a tissue sample for pre-treatment intra-tumoral assessment of proinflammatory and immunosuppressive factors. Preferably, tumor biopsies will be collected at the time of screening or newly obtained tissue can be used (no intervening treatment [local or systemic] involving the site of tissue biopsy once tissue biopsy is obtained up to the time of trial enrollment). Note: For cohort A, this refers to tissue obtained during fresh biopsy or archived postanti- PD-1/PD-L1 based therapy progression. For cohort B, this refers to newly diagnosed, all treatment naïve archival or fresh tissue. Additionally, for cohort A subjects, an archival sample (ideally treatment naïve) will be requested as well, however, enrollment is allowed for subjects unable to provide newly obtained or lacking tissue specimens after consultation with the Sponsor (see Table 7 of the protocol); 8. Have ECG with no clinically s
Exclusion criteria
Exclusion criteria: Cancer-specific Exclusion Criteria: 1. Any approved anti-cancer therapy including chemotherapy, targeted small molecule therapy or radiation therapy within 2 weeks prior to trial Day 0; or if subject has not recovered (ie., Less than or equal to grade 1 or returned to baseline level) from adverse events due to a previously administered agent; the following exceptions are allowed: - Palliative radiotherapy for bone metastases or soft tissue lesions should be completed > 7 days prior to baseline imaging; - Hormone-replacement therapy or oral contraceptives; - Subjects with grade 2 neuropathy or grade 2 alopecia; 2. Currently participating and receiving trial therapy or has participated in a trial of an investigational agent and/or has used an investigational device within 28 days prior to Day 0; Note: Subjects who have entered the follow-up phase of an investigational trial may participate as long as it has been 28 days since the last dose of the previous investigational agent or device. 3. Documented active or untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. For suspected neurological involvement, CT or MRI evaluation is recommended during screening to rule out CNS metastases. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurological symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. 4. Uncontrolled tumor-related pain - Subjects requiring pain medication must be on a stable regimen at trial entry. - Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should complete treatment at least 7 days prior to enrollment. - Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment. 5. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly and more frequently) o Subjects with indwelling catheters (e.g., PluerX) are allowed. 6. Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or Ca > 12 mg/dL or corrected serum calcium > ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab: - Subjects who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and do not have a history or clinically significant hypercalcemia are eligible. - Subjects who are receiving denosumab prior to enrollment must be willing and eligible to receive a bisphosphonate instead while in the trial. 7. Malignancies other than UCa within 3 years prior to Day 0, with the exception of t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: To evaluate the anti-tumor activity of INO-5401 + INO-9012 in combination with atezolizumab in subjects with locally advanced unresectable or metastatic/recurrent UCa;Timepoint(s) of evaluation of this end point: Please refer to Table 1: Trial Schedule of Events of Protocol, where it summarizes the trial procedures to be performed at each visit; Main Objective: 1. To determine the safety and tolerability of INO-5401 + INO-9012 delivered by IM injection followed by EP with CELLECTRA™ 2000 device in combination with atezolizumab among subjects with locally advanced unresectable or metastatic/recurrent UCa 2. To evaluate preliminary immune response to INO-5401 + INO-9012 in combination with atezolizumab in subjects with locally advanced unresectable or metastatic/recurrent UCa 3. To evaluate objective response rate of INO-5401 + INO-9012 in combination with atezolizumab in subjects who have received and/or progressed on anti-PD-1/PD-L1 based therapy previously (cohort A) ; Primary end point(s): - All adverse events (AEs) including adverse events of special interest (AESI) classified by system organ class (SOC), preferred term (PT), severity and relationship to drug - Clinically significant changes in safety laboratory parameters from baseline: CBC with Differential; Chemistry Panel; Urinalysis; T3, Free T4 and TSH; creatine phosphokinase (CPK) - Antigen-specific cellular immune responses that may be assessed by but not limited to: o Interferon-? secreting T lymphocytes in peripheral blood mononuclear cells (PBMCs) by ELI Spot - T-cell activation and cytolytic cell phenotype in PBMCs by Flow Cytometry or secretion of immune molecules - B cell activation/antibody secretion; - Assessment of Myeloid Derived Suppressor Cells (MDSC) - TCR sequencing of PBMCs for diversity and pu | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator review for treatment naïve, cisplatin-ineligible subjects (cohort B) - ORR by immune RECIST (iRECIST) for both cohorts - Duration of Response (DoR) for both cohorts - Progression Free Survival (PFS) as assessed by RECIST version 1.1 and iRECIST for both cohorts - Overall Survival (OS) for both cohorts ;Timepoint(s) of evaluation of this end point: Please refer to Table 1: Trial Schedule of Events of Protocol, where it summarizes the trial procedures to be performed at each visit | — |
Countries
Spain, United States
Contacts
Public ContactUCa-001 Trial Development
Inovio Pharmaceuticals, Inc.
Outcome results
None listed