A Study of the CDX-1307 Vaccine Regimen in Patients With Newly Diagnosed Muscle-Invasive Bladder Cancer (The N-ABLE Study)

Study Overview
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Brief Summary
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The major purpose of this study is to examine the anti-tumor activity of the CDX-1307 vaccine regimen when it is given before and after bladder cancer surgery. The study will also provide information about the safety of the vaccine regimen when given in combination with chemotherapy, and how it affects the immune systems.

Detailed Description
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CDX-1307 is an experimental vaccine that is designed to generate an immune response against a protein called human chorionic gonadotropin-beta (hCG-β). hCG-β is made by several types of cancers, including bladder cancer, and has been shown to be associated with shorter times to development of metastases and reduced survival in bladder cancer. In this study, it is hoped that administering the CDX-1307 vaccine will cause the body's immune system to attack bladder cancer cells in order to kill them or otherwise keep them from spreading or coming back. Standard treatment for early stage, muscle invasive bladder cancer includes the administration of chemotherapy to shrink the tumor followed by surgical removal of the bladder (cystectomy). This study will compare the effect of adding CDX-1307 administration to this standard treatment. CDX-1307 will be given with 3 different immune stimulants to try to increase the immune response against the tumor cells; collectively, this is called the CDX-1307 vaccine regimen. Only patients whose tumors make the hCG-β protein will be included in this study. Eligible patients will receive standard of care chemotherapy with the CDX-1307 vaccine regimen before surgery, and then CDX-1307 vaccine regimen alone (without chemotherapy) after surgery.

Official Title
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A Phase II, Open-Label Study of the CDX-1307 Vaccine Regimen as Neoadjuvant and Adjuvant Therapy in Patients With Newly Diagnosed Muscle-Invasive Bladder Cancer Expressing hCG-β

Conditions
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Bladder Cancer

Intervention / Treatment
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* Biological: CDX-1307 Vaccine Regimen
* Drug: Chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Among other criteria, patients must meet all of the following conditions to be eligible to be in the study: 18 years of age or older. Newly diagnosed muscle-invasive transitional cell (urothelial) bladder cancer where neoadjuvant chemotherapy and radical cystectomy with curative intent are indicated (i.e., American Joint Committee on Cancer (AJCC) stage T2-4a, Nany, M0). Patients must be entered into the study within eight weeks of their most recent diagnostic procedure, which is usually a diagnostic biopsy or transurethral resection of bladder tumor (TURBT) procedure. Histopathologically confirmed, transitional cell (urothelial) carcinoma. Urothelial tumors with mixed histology (but with <50% variant) are eligible. Tumor tissue (obtained during a prior procedure) confirmed to express hCG-β by a central laboratory. Candidate for therapy with neoadjuvant chemotherapy. Exclusion Criteria: Among other criteria, patients who meet any of the following conditions are NOT eligible to be in the study: Previous systemic chemotherapy or radiation for bladder cancer. Note: Prior immunotherapy or intravesical (administered within the bladder) chemotherapy for superficial disease is acceptable. History of anaphylactic reaction following exposure to humanized or human therapeutic monoclonal antibodies, hypersensitivity to GM-CSF or yeast derived products, clinically meaningful allergic reactions to imiquimod, resiquimod, or any known hypersensitivity or prior reaction to any of the formulation excipients in the study drugs. Concurrent chronic treatment with immunosuppressive or immunomodulatory agents, including any systemic steroid (exception: inhaled or topically applied steroids, and acute and chronic standard dose NSAIDs, are permitted). Known infection with HIV, HBV or HCV. Any underlying medical condition that, in the Investigator's opinion, will make the administration of study vaccine hazardous to the patient, would obscure the interpretation of adverse events, or would contraindicate receipt of neoadjuvant chemotherapy or surgical resection.

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: CDX-1307 Vaccine Regimen<br>Chemotherapy with CDX-1307 vaccine regimen (neoadjuvant phase), followed by bladder removal surgery (cystectomy). CDX-1307 vaccine regimen will continue to be given for up-to 1 year post-surgery (adjuvant/long-term follow-up phase). | Biological: CDX-1307 Vaccine Regimen<br>* CDX-1307 vaccine co-administered with immune adjuvants (GM-CSF, Poly-ICLC and Resiquimod)<br>Drug: Chemotherapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2 year Recurrence-Free Survival Rate | The 2-year recurrence-free survival rate will be estimated based on the proportion of patients who are classified as alive and without documented disease recurrence at this time point. | 2 years following enrollment | 
| Duration of Recurrence-Free Survival | The duration of recurrence-free survival is defined as the number of months from enrollment to the earlier of disease recurrence or death (whatever the cause). | Up-to 4 years after bladder removal surgery (cystectomy) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response to neoadjuvant chemotherapy | The tumor response to neoadjuvant chemotherapy will be evaluated as the proportion of patients who achieve a radiographic response as defined by the Response Evaluation Criteria for Solid Tumors (RECIST 1.1) or a pathologic complete response at cystectomy. | At cystectomy (anticipated to be about 4 months post-enrollment) | 
| Overall survival | Overall survival is defined as the number of months from enrollment to the date of death (whatever the cause). | Up-to 4 years following bladder removal surgery (cystecomy) | 
| Safety / Tolerability | The number and percentage of patients experiencing one or more adverse events will be summarized by relationship to study drug and severity. Separate tabulations will be provided for the neoadjuvant and adjuvant treatment phases. | Through completion of study treatment (about 1 year post-resection) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bladder cancer, immunotherapy, cystectomy, cancer vaccine, human chorionic gonadotropin, hCG, urogenital neoplasms, urinary bladder neoplasms, muscle invasive, non-metastatic, transitional cell (urothelial) bladder cancer