Bajorin, Dean F.;
Sharma, Padmanee;
Lerner, Seth P.;
Sims, Robert Brownell;
Sanders, Amanda;
DeVries, Todd;
Sheikh, Nadeem A.;
Gomella, Leonard G.
Preliminary safety, product parameters, and immune response assessments from a phase II randomized, open-label trial of DN24-02, an autologous cellular immunotherapy (ACI), in patients (pts) with surgically resected HER2+ urothelial cancer (UC) at high risk for recurrence
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Medientyp:
E-Artikel
Titel:
Preliminary safety, product parameters, and immune response assessments from a phase II randomized, open-label trial of DN24-02, an autologous cellular immunotherapy (ACI), in patients (pts) with surgically resected HER2+ urothelial cancer (UC) at high risk for recurrence
Beteiligte:
Bajorin, Dean F.;
Sharma, Padmanee;
Lerner, Seth P.;
Sims, Robert Brownell;
Sanders, Amanda;
DeVries, Todd;
Sheikh, Nadeem A.;
Gomella, Leonard G.
Erschienen:
American Society of Clinical Oncology (ASCO), 2013
Beschreibung:
<jats:p> 4547^ </jats:p><jats:p> Background: DN24-02 is a HER2-targeted ACI, consisting of antigen presenting cells (APC) cultured with BA7072, a recombinant HER2-derived antigen (HER500) linked to GM-CSF; DN24-02 is based on the same manufacturing platform as sipuleucel-T, approved for asymptomatic/minimally symptomatic metastatic castrate resistant prostate cancer. NeuACT (N10E1; NCT01353222) is an open-label, randomized phase 2 trial comparing adjuvant DN24E02 to surveillance in HER2+ UC pts at high risk of relapse following cystectomy or nephroureterectomy. The primary endpoint is overall survival. Here we report preliminary evaluation of adverse events (AE), product potency, and immune response. Methods: Pts randomized to DN24-02 underwent leukapheresis followed by infusion of DN24-02 (total of 3 infusions with 2 wk intervals). AEs were assessed at each visit. Product potency was assessed for each infusion by measuring CD54 upregulation on APCs, a marker of APC activation. Antigen-specific immune responses were evaluated by ELISA to HER500 and BA7072. Results: As of November 2012, 13 pts had received ≥1 DN24-02 infusion. The most commonly reported AEs within 1 day after DN24-02 infusion were mild–moderate chills (54%), nausea (31%) and fatigue (23%). Ten pts completed all DN24-02 infusions and were assessed for product potency. Increased median APC activation at infusions 2 and 3 compared with infusion 1 was indicative of an immunological prime-boost effect; this effect was also seen in the 7/10 pts with prior neoadjuvant chemotherapy. Median anti-BA7072 and anti-HER500 titers (IgM) were 128- and 256-fold higher at week 6 vs baseline, respectively. The emergence of IgG indicated a memory antibody phenotype. Conclusions: Preliminary data indicate that DN24-02 product potency (CD54 upregulation) is comparable to sipuleucel-T. DN24-02 appears to be well tolerated in UC. Favorable immune responses were observed, including in pts with prior neoadjuvant chemotherapy. Updated results, including preliminary T-cell immune response data, will be presented. Clinical trial information: NCT01353222. </jats:p>