NeuACT, a phase II, randomized, open-label trial of DN24-02: Updated analysis of HER2 expression, immune responses, product parameters, and safety in patients with surgically resected HER2+ urothelial cancer

296^ Background: DN24-02 is an investigational autologous cellular immunotherapy (ACI) consisting of antigen presenting cells (APCs) cultured with BA7072, a recombinant HER2-derived antigen (HER500) linked to granulocyte-macrophage colony-stimulating factor. In the ongoing NeuACT (N10-1; NCT01353222) trial, patients (pts) with high-risk, HER2+ urothelial cancer (UC) are randomized 1:1 to either adjuvant DN24-02 or surveillance. Updated analyses are presented. Methods: Eligibility criteria include radical surgical resection of primary ≥pT2 or pN+ UC (bladder or upper tract) with HER2 expression ≥1+ by immunohistochemistry. Pts randomized to DN24-02 undergo 3 cycles of leukapheresis and infusion at 2-week intervals. Product potency is assessed at each infusion. Immune responses and adverse events (AEs) are measured at multiple time points. Results: By July 2013, tumor specimens from 226 pts had been screened. Of these, 75% (95% CI 69–81%) had HER2 expression of ≥1+ in the primary tumor, 32% had ≥2+ and 8% had 3+. In pts with available lymph node samples (n=83), 84% (95% CI 75–91%) had a HER2 score of ≥1+ in the lymph nodes; 49% and 14% had ≥2+ and 3+, respectively. Pts with 1+ HER2 expression had similar immune responses to BA7072 as those with higher HER2 levels. APC activation (CD54 upregulation) was observed at each infusion in the first 30 pts who had completed the 3 infusions, but was typically greater at infusions 2 (median 15.56; range: 6.42–23.97) and 3 (14.69; 8.24–30.86) than infusion 1 (7.35; 4.04–14.34). In the 5 pts with available data, BA7072 and HER500 specific antibody responses increased from baseline for at least 12 months. Most (92.3%) AEs were grade 1–2 in severity, including all AEs that occurred ≤1 day after infusion. Conclusions: The high frequencies (≥75%) of ≥1+ HER2 scores in primary tumor and lymph node samples confirm that HER2 expression is common in muscle-invasive and node+ UC. DN24-02 product potency data suggest an immunologic prime-boost effect. The observed humoral responses are the first data suggesting prolonged immune responses with an ACI in UC. Most AEs were grade 1–2 in severity. Clinical trial information: NCT01353222.