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