Study of CG0070 Given in Combination With Pembrolizumab, in Non-Muscle Invasive Bladder Cancer, Unresponsive to Bacillus Calmette-Guerin

Study Overview
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Brief Summary
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To evaluate the activity of intravesical administration of CG0070 and intravenous administration of Pembrolizumab in patients with tissue pathology-confirmed non-muscular invasive bladder cancer (NMIBC) who have Bacillus-Calmette-Guerin (BCG) unresponsive disease with carcinoma in situ (CIS) with or without Ta/T1 papillary disease.

Detailed Description
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An opened label trial designed to evaluate CG0070 and DDM in combination with Pembrolizumab in patients with NMIBC who have failed prior BCG therapy. The target population of 37 subjects with CIS with or without concomitant high-grade Ta or T1 papillary disease will be enrolled. BCG failure is defined as persistent or recurrent disease within 12 months of completion of adequate BCG therapy.

Official Title
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A Phase 2, Single Arm Study of CG0070 Combined With Pembrolizumab in Patients With Non Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Bacillus Calmette-Guerin (BCG)

Conditions
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Non Muscle Invasive Bladder Cancer

Intervention / Treatment
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* Biological: CG0070
* Biological: Pembrolizumab Injection
* Other: n-dodecyl-B-D-maltoside


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 Pathologically confirmed NMIBC with CIS (with or without Ta/T1 disease) Unresponsive to prior BCG therapy (Lerner 2015) defined as persistent or recurrent CIS alone or with recurrent Ta/T1 (noninvasive papillary disease/tumor invades the sub- epithelial connective tissue) disease within 12 months of completion of adequate BCG therapy. An assessment within 15 months can also qualify when no assessment was performed within 12 months after completion of adequate BCG therapy. Adequate BCG is defined as at least 5 treatments with induction BCG followed by at least 2 BCG treatments as reinduction or maintenance Ineligible for radical cystectomy or refusal of radical cystectomy Adequate organ function Key Exclusion Criteria: Immuno-deficient due to chronic steroid or other immunosuppressant use, HIV, or prior organ transplant Prior treatment with adenovirus-based cancer therapy Prior therapy with or intolerant to prior checkpoint inhibitor therapy Clinically significant or active cardiac disease Active autoimmune disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm<br>CG0070 will be administered intravesically (IVE) following a sequence of bladder washes with 5% DDM and normal saline. CG0070 will be administered weekly x 6 on Day 1 to Week 6. If the patient shows persistent high-grade disease at Week 12, the patient will receive another cycle of 6 weekly treatments. If there is no disease present at Week 12 (e.g., complete response) then the patient will receive 3 weekly treatments. Beginning at Week 24, patients will receive weekly x 3 treatments every 3 months through Week 48 then every 24 weeks thereafter. Pembrolizumab will be given intravenous (IV) concurrently starting on Day 1 and continue every 3 weeks for up to 2 years. | Biological: CG0070<br>* Engineered Oncolytic Adenovirus<br>Biological: Pembrolizumab Injection<br>* Immune checkpoint inhibitor, Monoclonal antibody<br>* Other names: Keytruda;Other: n-dodecyl-B-D-maltoside<br>* Transduction-enhancing agent.<br>* Other names: DDM;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate in patients | Percentage of patients with a complete response as defined by FDA guidance document dated February 2018 for NMIBC. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events when CG0070 administered intravesically when combined with pembrolizumab. | Percentage of patients with adverse events by grade as determined by NCI CTCAE v5.0 | 12 months | 
| Median duration of response (DoR) | Median duration of response in patients with a CR or PR | 12 months | 
| Median overall survival (OS) | Median overall survival in months in patients | 12 months | 
| Median progression free survival | Median duration of progression free survival of patients | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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high-grade Ta papillary disease, high-grade T1 papillary disease, carcinoma in situ, Bacillus-Calmette-Guerin Unresponsive