DN24-02 as Adjuvant Therapy in Subjects With High Risk HER2+ Urothelial Carcinoma

Study Overview
=================
Brief Summary
-----------------
This study was conducted to examine survival, disease-free survival, safety, and the magnitude of the immune response induced following administration of DN24-02 in subjects with HER2+ urothelial carcinoma.

Detailed Description
-----------------
Multicenter, open-label, Phase 2 study. Subjects were randomized to either the investigational product, DN24-02, or to standard of care. Subjects randomized to the experimental arm received DN24-02 at 2-week intervals, for a total of 3 infusions. The study evaluated survival, disease-free survival, safety and the magnitude of the immune response between these 2 subject groups.

Official Title
-----------------
A Randomized, Phase 2, Open-label Study Evaluating DN24-02 as Adjuvant Therapy in Subjects With High Risk HER2+ Urothelial Carcinoma

Conditions
-----------------
Urothelial Carcinoma

Intervention / Treatment
-----------------
* Biological: DN24-02
* Other: Standard of Care


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histopathologic evidence of urothelial carcinoma, based on local pathology report. High risk urothelial carcinoma, in subjects with or without prior neoadjuvant chemotherapy, defined as positive lymph node status (N+), or pathological stage ≥ pathological tumor (pT2) in patients who either have negative lymph node status (N0) or have no evaluable lymph nodes (Nx). Radical surgical resection was performed ≤ 84 days (12 weeks) prior to registration. No evidence of residual disease or metastasis following surgical resection which includes: absence of invasive cancer at the margins in the surgical specimens and confirmation by CT scan of chest, abdomen and pelvis obtained at least 28 days following surgical resection and ≤ 28 days prior to registration. HER2/neu tissue expression ≥ 1+ by immunohistochemistry (IHC). Available biopsy specimens from the primary tumor and involved lymph nodes are be submitted to the central pathology laboratory prior to registration for confirmation of HER2/neu tissue expression. Last neoadjuvant chemotherapy treatment administered at least 60 days prior to registration. Left ventricular ejection fraction ≥ 50% on multigated acquisition (MUGA) scan or echocardiogram obtained at least 28 days following surgery and ≤ 28 days prior to registration. Women of child-bearing potential have a negative serum pregnancy test result ≤ 28 days prior to registration and agree not to breastfeed during investigational treatment with DN24-02 and for 28 days following the final infusion of DN24-02. All males and premenopausal females who have not been surgically sterilized have agreed to practice a method of birth control considered by the Investigator to be effective and medically acceptable for at least 14 days prior to registration, throughout treatment, and for 28 days following the final infusion of DN24-02. Adequate hematologic, renal, and liver function. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. Exclusion Criteria: A history of stage III or greater non-urothelial cancer. Exceptions include: Subject with basal or squamous cell skin cancers that has been adequately treated who are disease-free at the time of registration. Subjects who have been disease-free and off treatment for ≥ 10 years at the time of registration. A history of stage I or II non-urothelial cancer. Exceptions include: Subjects who have been disease-free and off treatment for ≥ 3 years at the time of registration. Subjects with incidental prostate cancer diagnosed at the time of cystoprostatectomy. Subjects with basal or squamous cell skin cancer. Partial cystectomy in the setting of bladder cancer primary tumor. Partial nephrectomy in the setting of renal pelvis primary tumor. Adjuvant systemic therapy for urothelial or prostatic carcinoma following surgical resection. Adjuvant radiation therapy for urothelial or prostatic carcinoma following surgical resection. Incidental prostate cancer with detectable post-operative (radical cystoprostatectomy) prostate specific antigen (PSA) levels ≤ 28 days prior to registration. Any major surgery (e.g., surgery requiring general anesthesia) ≤ 28 days prior to registration. Systemic treatment on any investigational clinical trial ≤ 28 days prior to registration. Systemic glucocorticoid or immunosuppressive therapy use ≤ 28 days prior to registration. Any infection requiring parenteral antibiotic therapy or causing fever (i.e., temperature > 100.5°F or > 38.1°C) ≤ 7 days prior to registration. A history of allergic reactions attributed to compounds of similar chemical or biologic composition to DN24-02 or Granulocyte-macrophage colony-stimulating factor (GM-CSF). Any medical intervention, has any other condition, or has any other circumstance which, in the opinion of the Investigator or the Dendreon Medical Monitor, could compromise adherence with study requirements or otherwise compromise the study's objectives.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DN24-02<br>Subjects received infusion of DN24-02, at 2-week intervals, for a total of 3 infusions. | Biological: DN24-02<br>* DN24-02 is an autologous cellular immunotherapy product designed to stimulate an immune response against HER2/neu. It consists of autologous peripheral blood mononuclear cells (PBMCs), including antigen presenting cells (APCs), which are activated ex vivo with a recombinant fusion protein, BA7072.<br>|
| Other: Standard of Care<br>Subjects randomized to the control arm were treated per standard of care, which in this patient population is generally observation, as there is currently no evidence that treatment with non-cisplatin containing chemotherapy is beneficial in the adjuvant setting for this patient population. | Other: Standard of Care<br>* Observation only until documentation of disease recurrence.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival is defined as the time from randomization to death due to any cause. *This study was terminated early due to administrative reasons. | Subjects will be followed from baseline through the remainder of their lives or until study completion (approximately 60 months) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vaccine, Bladder cancer, Renal pelvis cancer, Ureteral cancer, Urethral cancer, Bladder, Renal pelvis, Ureter, Urethra, Immune therapy, Immunotherapy, Dendritic cells, Antigen-presenting cells, Antigen presenting cells, Cancer vaccine, Urothelial carcinoma, Urothelial neoplasms, Neoplasms by site, Neoplasms