Antigen Presenting Cell Based Immunotherapy Targeting Her2/Neu Positive Solid Tumors: Results of A Phase 1 Study of Apc8024.

2528 Background: APC8024 is a cellular vaccine therapy derived from autologous antigen (Ag) presenting cells (APC) loaded ex vivo with the HER2/Neu tumor Ag HER500/GM-CSF, designated BA7072. The BA7072 Ag consists of recombinant sequences of the extracellular and intracellular domain of HER2 fused to GM-CSF Methods: Patients (pts) with metastatic solid tumors that were HER2 (+) were eligible. Autologous mononuclear cells were collected and APC precursors were isolated and then loaded with the fusion protein BA7072. The concentration of BA7072 in culture was either 10μg/ml or 40μg/ml. The loaded APCs were collected, fresh cells were reinfused at Week 0, and aliquots were cryopreserved. Thawed cells were then reinfused at Weeks 2 and 4. A total of 1 x 109 cells were reinfused at each time point. Pts were followed without further therapy until either Week 52 or documented disease progression, whichever occurred first. Immune response (IR) was evaluated at Weeks 0, 4, 8, and 16. Results: Ten pts (8 females, 2 males) received vaccine therapy and were evaluable. The mean age was 55 (range 34–76). All pts had advanced, metastatic disease and had received a mean of 3 prior chemotherapy regimens (range 0–6). All pts were HER2/Neu positive (1–3+) by IHC. Cancer types included ovarian (4), colorectal (3), and breast (3). The treatment was generally well tolerated. The adverse events (AE) most frequently associated with APC8024 were fatigue (n=5), rigors (n=5), and pyrexia (n=2), all of which were Grade 1–2. All higher grade and serious AEs were judged to be unrelated to the therapy. An antigen specific T cell response, as measured by IFNγ ELISPOT and T cell proliferation, was induced after treatment compared to baseline (ELISPOT P=0.0153, Proliferation P<0.0001). Based on the investigator's assessment, 2 subjects had stable disease for 16 and 24 weeks. Both subjects had Stage 4 ovarian cancer, and had been heavily pretreated. Conclusions: APC8024 was a safe and well tolerated cellular vaccine therapy in this Phase 1 study. The robust T cell IR data supports further evaluation of administration of frozen/thawed product. Phase 2 studies in breast cancer are planned. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Dendreon Corp. Dendreon Corp. Dendreon Corp.