Abstract B001: Preliminary clinical activity and safety of an autologous AdHER2 dendritic cell vaccine in patients with advanced metastatic HER2+ solid tumors
Authors: Wood Lauren V. , Roberson Brenda D. , Agarwal Piyush , Apolo Andrea A. , Stroncek David , Weiner Lou M. , Morris John C. , Steel Jason C. , Terabe Masaki , Lee MIn-Jung , Trepel Jane , Shim Sohee , Berzofsky Jay A. 
Published: November 2016

Abstract
Background: In HER2-expressing mouse tumor models we achieved cure of large established tumors using an adenoviral vector vaccine expressing the HER2 extracellular and transmembrane (ECTM) domains that was mediated by the induction of anti-HER2 antibodies. Here we report clinical translation of this vaccine utilizing a therapeutic autologous adenoviral transduced dendritic cell (DC) vaccine expressing human HER2 EC and TM domains (AdHER2ECTM) in adults with advanced metastatic tumors and muscle-invasive bladder cancer (MIBC) post cystectomy, with with 1-3+ HER2 expression by immunohistochemistry (IHC).
Methods: In this two-part phase I study (NCT01730118) subjects with HER2+ metastatic solid tumors naïve to HER2-targeted therapies received up to 5 doses of the AdHER2 DC vaccine at Weeks 0, 4, 8, 16 and 24. Dose escalation occurred in 3 cohorts of 6 patients utilizing 5, 10 or 20×106 viable AdHER2ECTM transduced DCs per dose, respectively. Cohorts 1-3 have been completed without dose-limiting or cardiac toxicity. Enrollment has been initiated in an Expansion Cohort with further dose escalation to 40×106 viable DCs per vaccine. MIBC patients were enrolled and received vaccination in the adjuvant setting after 12-week safety was documented in ≥ 10 treated patients. Response was assessed using immune-related response criteria (irRC).
Results: A total of 21 patients (7 with colon, 5 ovarian, 3 bladder and 6 other cancers), median age 60 yrs (range, 36-72 yrs) with a median of 3 prior treatment regimens received ≥ 2 vaccine doses (median 4) (range 2-5): 14F, 7M; HER2 IHC: 1+ N = 6, 2+ N = 8, 3+ N = 7. Patients that received all 5 scheduled vaccines in Cohorts 1, 2 and 3 were 0 of 6, 2 of 6 and 4 of 6, respectively. Among patients with metastatic disease, the following responses were observed: Cohort 1: No responses; Cohort 2: 1 partial response (PR) in a gastroesophageal cancer patient (-71% lasting 44 weeks), stable disease (SD) in 2 colon cancer patients lasting 24 and 28 weeks; Cohort 3: 1 complete response (CR) (ongoing at 52 weeks) in an ovarian cancer patient, and 1 SD (ongoing at 36 weeks), also in a patient with ovarian cancer, by irRC. Indeed, in dose Cohorts 2 and 3, 5 of 10 metastatic patients had a CR, PR or SD for an overall disease control rate of 50%. Responses were seen in subjects with all ranges of HER2 expression. MIBC patients remain without disease at 48 and 60 weeks. Adverse events were limited to injection site reactions (all ≤ G2) and no cardiac safety signal has been detected to date with serial monitoring of LVEF by echocardiogram and serum Troponin T levels. Decreases in circulating tumor cells (CTCs) were observed at 12 weeks in 6 of 16 (38%) of patients examined, including 3 of the 5 patients exhibiting disease control. Analyses of anti-HER2 antibody titers and epitope repertoire are ongoing.
Conclusion: AdHER2 DC vaccination is safe, well tolerated and is associated with anti-tumor activity, including decreases in circulating tumor cells.
Citation Format: Lauren V. Wood, Brenda D. Roberson, Piyush Agarwal, Andrea A. Apolo, David Stroncek, Lou M. Weiner, John C. Morris, Jason C. Steel, Masaki Terabe, MIn-Jung Lee, Jane Trepel, Sohee Shim, Jay A. Berzofsky. Preliminary clinical activity and safety of an autologous AdHER2 dendritic cell vaccine in patients with advanced metastatic HER2+ solid tumors [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B001.