Abstract P2-15-03: A Phase Ib Study of an adjuvant GM-CSF-Secreting Breast Cancer Vaccine

Background: Vaccination with tumor cells engineered to secrete granulocyte-macrophage colony stimulating factor (GM-CSF) generates potent, specific, and long-lasting anti-tumor immunity in multiple tumor models. Here, we present analysis on the safety, feasibility, and biologic activity of an autologous GM-CSF-secreting breast cancer vaccine in the high-risk adjuvant setting. Methods: Following IRB approval and patient consent, 18 patients with stage II-III breast cancer underwent tumor procurement for vaccine development at the time of breast surgery. Patients were required to have at least 4 cm of primary tumor, or have received neoadjuvant chemotherapy with at least 2 cm of residual tumor. 11 patients had insufficient tumor following neoadjuvant chemotherapy. 7 patients had sufficient tumor harvested to produce and subsequently receive vaccine therapy. Breast cancer cells were transduced with a replication defective adenoviral vector encoding GM-CSF and irradiated. Vaccinations were started 4-12 weeks after completion of all chemotherapy, immunotherapy, and radiation therapy. Vaccines were delivered subcutaneously (sc) and intradermally (id) weekly for three weeks, then every other week for a total of 6 doses. Immune monitoring included skin biopsies of vaccine sites, measurement of leukocyte populations, and proteomic-based assessment of antibody responses. Results: Tumor cell yields ranged from 0.07-31.6 x 10 6 cells. Dose levels were based on cellular yield, ranging from 10 5 - 4 x10 6 cells/dose for the 7 patients with sufficient cell numbers. Vaccinated patients were 32-65 years of age, and all received 6 vaccines total. Three patients developed relapse within one year of the start of vaccinations, one of whom died at 14 months. The remaining four patients remained disease-free 23-34 months from start of vaccine. Toxicities related to treatment were mild and included Grade I/II local injection-site reactions, as well as grade I/II fatigue, fever, upper respiratory symptoms, cough, and joint pain. One episode of grade 3 fatigue was observed. Increases in antibody responses (p Conclusion: For larger tumors, breast cancer cells can be harvested from a subset of patients in sufficient number for autologous vaccine production at the time of breast surgery. Autologous vaccination can induce immune responses with limited toxicity. The proteomic-based identification of antigen-specific immune responses following vaccination will be presented. Citation Format: Karen S Anderson, Beth Overmoyer, Christine Canning, Jennifer Savoie, Garrick Wallstrom, Eric P Winer, Glenn Dranoff. A Phase Ib Study of an adjuvant GM-CSF-Secreting Breast Cancer Vaccine [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-15-03.