Association Of Autologous Adher2 Dendritic Cell Vaccination With Antitumor Activity And Number Of Circulating Tumor Cells.

3089 Background: We achieved cure of large established tumors in syngeneic BALB/c mice using an adenoviral vector vaccine expressing rodent HER2 extracellular (EC) and transmembrane (TM) domains mediated by the induction of anti-HER2 antibodies. We report clinical translation utilizing an autologous adenoviral- transduced dendritic cell (DC) vaccine expressing human HER2 EC and TM domains (AdHER2ECTM) in adults with advanced metastatic tumors with 1-3+ HER2 expression. Methods: In this two-part phase I study (NCT01730118) subjects with HER2+ metastatic solid tumors naïve to HER2-targeted therapies (Part 1) or HER2+ treatment-experienced breast cancer (Part 2) received 5 doses of vaccine at Weeks 0, 4, 8, 16 and 24. Part 1 dose escalation involved 3 cohorts of 6 patients utilizing 5x10 6 , 10x10 6 and 20x10 6 viable DCs per dose, respectively. With no DLTs or evidence of cardiac toxicity, dose escalation to 40x10 6 viable DCs per dose was allowed in the Part 1 Expansion Cohort and Part 2 treatment was begun at a starting dose of 20x10 6 viable DCs per vaccine. Adjuvant muscle-invasive bladder cancer patients were allowed to enroll with safety documented out to 12 weeks in > 10 treated patients. Re-staging was assessed using immune-related response criteria (irRC). Remaining study accrual: Part 1 (N = 9), Part 2 (N = 24). Results: A total of 27 cancer patients (7 colon, 6 breast, 5 ovarian, 3 bladder, 6 other) have received > 2 vaccine doses (median 4): 19F, 8M, median age 60 yrs, median 3 prior treatment regimens (range 1-11); HER2 IHC 1+ N = 6, 2+ N = 9, 3+ N = 12. Of metastatic patients receiving 10x10 6 viable DCs per dose or higher, 7 of 19 (37%) had evidence of response by irRC: 1 CR (ongoing at 100 weeks), 1 PR (-71% lasting 44 weeks) and 5 SD (median duration 24 weeks, range 8 to 48 weeks). Two adjuvant bladder cancer patients remain without disease at 100 weeks. Adverse events were limited to local injection site reactions < G2. Of patients with paired baseline samples, 40% (8/20), 83% (5/6) and 100% (2/2) exhibited decreases in circulating tumor cells at 12, 28 and 48 weeks, respectively. Conclusions: AdHER2 DC vaccination is safe and is associated with evidence of clinical benefit and anti-tumor activity. Clinical trial information: NCT01730118.