Recently, the aggressive intervention of multidisciplinary therapy has resulted in improving the life prognosis of pediatric solid tumors. However, in the pediatric patients with metastatic or refractory solid tumors, the prognosis remains poor. Additionally, various critical, late complications could continue to occur. Therefore, the development of novel, effective therapy is urgently required. Immunotherapy could be the one of effective therapeutic strategy for pediatric solid tumors. Actually, the KOC1, FOXM1, and KIF20A might be capable of being an ideal target of anticancer immunotherapy against pediatric solid tumors that highly had expression of these cancer antigens. In this nonrandomized, open-label, phase I clinical trial, we analyzed the safety and efficacy of NCCV cocktail 1 vaccine, a cocktail of cancer peptides derived from KOC1, FOXM1, and KIF20A, in patients with pediatric solid tumors. Experimental Design: Twelve patients with refractory pediatric solid tumors, including 3 patients with neuroblastoma, 2 patients with Ewing’s sarcoma, 5 patients with rhabdomyosarcoma, and 2 patients with osteosarcoma, underwent NCCV cocktail 1 vaccination (intradermal injections every a week). In 9 enrolled patients, the histologic expression of KOC1, FOXM1, and KIF20A before vaccination were evaluated using tissue specimen obtained from biopsy or surgery. The primary endpoint was the safety of NCCV cocktail 1 vaccination. The secondary endpoints were immune response, as measured by in vivo and in vitro interferon (IFN)-r enzyme-linked immunospot (ELISPOT) assay and Dextramer assay, and the clinical outcomes of tumor response and progression free survival (PFS).Results:No dose-limiting toxicity (DLT) was observed in this trial, and we suggested that NCCV cocktail 1 vaccination was well-tolerated. Of nine patients, 6 patients (66.7%), 6 patients (66.7%), and 7 patients (77.8%), exhibited positive expression of KOC1, FOXM1, and KIF20A before vaccination, respectively. Of eleven patients, 4 patients (36.4%), 8 patients (72.7%), and 5 patients (45.5%) were induced peptide-specific CTL response of KOC, FOXM1, and KIF20A by NCCV cocktail 1 vaccine, respectively. Also, 4 patients showed stable disease after 8 weeks, and 2 patients showed during of remission for more than 11 months after second complete remission. Additionally, patients with high peptide-specific CTL frequencies of all KOC, FOXM1, and KIF20A (n=4) had better PFS than those with low frequencies (n=7) by Kaplan-Meier analysis (log-rank test, P =0.019). By Cox proportional hazard models, univariate and multivariate analysis indicated that only induction of peptide specific CTL in all of these three antigens was independent factor related to PFS (P = 0.039; HR = 5.60; 95% CI 1.09-28.91, P = 0.050; HR = 6.00; 95% CI 1.00-36.32, respectively). Conclusions:The results of this trial demonstrated that the NCCV cocktail 1 vaccine was safe and had ability to induce some degree of immune response, which could result in the benefit for preventing the recurrence of pediatric solid tumors, especially after a second complete remission.

Citation Format: Yu Akazawa, Ako Hosono, Toshiaki Yoshikawa, Hide Kaneda, Junichi Hara, Yoshiaki Kinoshita, Kenichi Kohashi, Atsushi Manabe, Yoko Shioda, Kayoko Shoda, Manami Shimomura, Shoichi Mizuno, Yasunari Nakamoto, Tetsuya Nakatsura. Phase I study of vaccine therapy with a cocktail of peptides for pediatric patients with refractory solid tumors [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A001.