Design of a phase II randomized, open-label trial of DN24-02, an autologous cellular immunotherapy targeting HER2/neu, in patients with surgically resected urothelial cancer at high risk of recurrence.

Abstract

TPS4673 Background: Despite surgical resection and the use of (neo)adjuvant chemotherapy, up to 50% of patients with invasive urothelial carcinoma will have disease recurrence and eventually die of metastatic disease. New approaches are needed for these patients. Approximately 50% of patients with high-risk pathologic features have evidence of HER2 expression in the primary tumor or involved lymph nodes. DN24-02 is an autologous cellular immunotherapy targeting HER2, which is based on Dendreon’s Antigen Delivery Cassette technology – the same platform used for sipuleucel-T (an FDA-approved treatment for asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer). Each dose of DN24-02 is manufactured by culture of peripheral blood mononuclear cells obtained by leukapheresis with a recombinant antigen that comprises components of the intra- and extracellular domains of the HER2 antigen linked to GM-CSF. A product similar to DN24-02 has shown evidence of safety and immune response in phase I studies. Objectives: The primary objective is to determine whether DN24-02, given as adjuvant therapy following surgical resection, can prolong survival compared to standard of care (SOC). Secondary objectives are to evaluate disease-free survival, safety, and immune responses to DN24-02. Methods: Eligible patients will have undergone surgical resection of a primary urothelial cancer, with either ≥pT2 or pN+ staging, and HER2 expression ≥1+ by IHC based on pathologic review. Approximately 180 patients will be randomized (1:1) to receive three IV infusions of DN24-02 as adjuvant therapy approximately every 2 weeks, or SOC. Stratification will include 1) neoadjuvant chemotherapy vs surgery alone; and 2) positive (pN+) vs negative lymph node involvement (pN0). Other adjuvant chemotherapy will not be allowed. Patients can be treated per SOC if there is disease recurrence. Patients will be monitored for evidence of recurrence by imaging, and followed for survival. Cellular and serological immune responses will be assessed at baseline and post-DN24-02 therapy.