BETHESDA, MD USA (UroToday.com) - Introduction and Objectives: HER2 overexpression in high-risk UC patients may be a negative prognostic factor.
DN24-02 is an investigational HER2-targeted autologous cellular immunotherapy consisting of antigen presenting cells (APCs) cultured with BA7072, a recombinant HER2-derived antigen linked to GM-CSF. NeuACT (N10-1; NCT01353222) compares adjuvant DN24-02 to surveillance in HER2+ UC patients at high risk of relapse. The primary endpoint is overall survival; enrollment is ongoing. Updated HER2 expression, product potency and safety data are presented.
Methods: Eligibility criteria include radical surgical resection of a primary UC (bladder or upper tract), with either ≥ pT2 or pN+ staging and HER2 expression ≥ 1+ by immunohistochemistry (IHC). Patients randomized to DN24-02 undergo leukapheresis for each of the 3 DN24-02 infusions given at 2-week intervals. Product potency is assessed by APC activation (ratio of CD54 expression on post- and pre-culture cells). Cellular and humoral immune responses are measured at multiple time points. Adverse events (AEs) are assessed using CTCAE v4.03. The trial is funded by Dendreon.
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Results: As of July 2013, tumor specimens from 226 pts had been screened. Of these, 75% (95% CI: 69–81%) had HER2 expression score ≥ 1+ (by IHC) in the primary tumor, with 32% having a ≥ 2+ score and 8% having a 3+ score. HER2 expression levels were evaluated in the 37% of patients with available lymph node samples: 84% (95% CI: 75–91%) had a score ≥ 1+ in the lymph nodes, with 49% and 14% with ≥ 2+ and 3+ scores, respectively. Nodal stage and lymph node HER2 expression correlated (p=0.025). Patients with HER2 expression of 1+ appear to have comparable levels of immune response to BA7072 as those with higher HER2 levels. Product potency was assessed in 21 pts who have completed DN24-02 therapy. APC activation was observed for all 3 infusions but was typically greater at infusions 2 (median 14.97; range: 6.48–23.97) and 3 (14.50; 8.24–21.80) vs infusion 1 (7.01; 4.04–14.34). The most common AEs (> 20% of pts) were chills (44%), fatigue (40%), nausea (36%), vomiting (24%) and headache (24%); most occurred ≤ 1 day after infusion.
Conclusions: The trial suggests high frequencies (≥ 75%) of HER2 expression ≥ 1+ in primary tumor and lymph node samples, confirming HER2 expression is common in UC. These preliminary analyses suggest that DN24-02 product potency is indicative of an immunologic prime-boost effect, and most AEs are infusion-related occurring ≤1 day after infusion.
Presented by:
Gomella LG,1 Sharma P,2 Quinn D,3 Lerner S,4 Press MF,3 Sims R,5 DeVries T5 Sheikh N,5 Chen M,5 Locker M,5 Bajorin D6
1Jefferson Medical College and Kimmel Cancer Center, Philadelphia, PA, USA; 2University of Texas MD Anderson Cancer Center, Houston, TX, USA; 3University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA; 4Baylor College of Medicine, The Scott Department of Urology, Houston, TX, USA; 5Dendreon Corporation, Seattle, WA, USA; 6Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Presented at the 14th Annual Meeting of the Society of Urologic Oncology (SUO) "Extraordinary Opportunities for Discovery" - December 4 - 6, 2013 - Bethesda, MD USA