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Publication of the results of YNP01 Phase I study of CYT001

The results of the specified clinical trial “A phase I study of combination immunotherapy with HSP70 derived peptide, GPC3 derived peptide, IMP321 and Hiltonol for patients with advanced or metastatic solid cancer” (YNP01 study) of CYT001 were published in Cancer Immunology, Immunotherapy (On-line article).
This First-in-Human phase I study was performed to evaluate the safety, peptide-specific immune responses, and antitumor effects of vaccination therapy comprising multi-HLA-binding HSP70/ glypican-3 peptides and a novel adjuvant combination of Poly-ICLC and LAG-3Ig. AI-designed peptide prediction enabled the discovery of multi-HLA binding and immunogenic epitope peptides, and the combination of Poly-ICLC and LAG-3Ig are expected to boost antitumor effects of these multi-HLA peptides synergistically.
The trial was a dose escalation study in three-patient cohorts, enrolled 11 patients at the recommended dose. Approximately 70% of patients showed a CTL response to each peptide, and more than half patients showed a strong CTL response in one month at the recommended dose. Further notable results were observed at the recommended dose, including significant reduction of lymphocyte population expressing an exhaustion marker, i.e., TIM3+ CD4 T cells, in peripheral blood and an overall survival of 18 months or more in 5 patients out of 11 patients.
The recommended dose of CYT001 derived from this study has been adopted in the Investigator-Initiated Phase I Trial (CRESCENT1).
Cytlimic continues to advance the development of CYT001 through collaborations with medical centers, based on the results and knowledges gained from the YNP01 study.
Abstract titles, authors and abstracts are:
Title: A phase I study of multi-HLA binding peptides derived from heat shock protein 70/glypican-3 and a novel combination adjuvant of hLAG-3Ig and Poly-ICLC for patients with metastatic gastrointestinal cancers: YNP01 trial
Authors: Masao Nakajima1, Shoichi Hazama2, Koji Tamada3, Keiko Udaka4, Yasunari Kouki5, Toshinari Uematsu5, Hideki Arima5, Akira Saito6, Tomoya Miyakawa7, Shun Doi8, Hiroto Matsui1, Yoshitaro Shindo1, Shinsuke Kanekiyo1, Yukio Tokumitsu1, Shinobu Tomochika1, Michihisa Iida1, Shin Yoshida1, Nobuaki Suzuki1, Shigeru Takeda1, Shigefumi Yoshino9, Tomio Ueno10, Hiroaki Nagano1
  1. Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
  2. Department of Translational Research and Developmental Therapeutics against Cancer, Yamaguchi University School of Medicine, Ube, Japan
  3. Department of Immunology, Yamaguchi University Graduate School of Medicine, Ube, Japan
  4. Department of Immunology, Kochi Medical School, Nankoku, Japan
  5. Department of Pharmacy, Yamaguchi University Hospital, Ube, Japan
  6. Department of Pathology, Tokyo Medical University, Tokyo, Japan
  7. NEC Corporation, Tokyo, Japan
  8. CYTLIMIC Inc., Tokyo, Japan
  9. Oncology Center, Yamaguchi University Hospital, Ube, Japan
  10. Department of Digestive Surgery, Kawasaki University School of Medicine, Kurashiki, Japan
 
 
Abstract:
BACKGROUND: This phase I study aimed to evaluate the safety, peptide-specific immune responses, and antitumor effects of a novel vaccination therapy comprising multi-HLA-binding heat shock protein (HSP) 70/ glypican-3 (GPC3) peptides and a novel adjuvant combination of hLAG-3Ig and Poly-ICLC against metastatic gastrointestinal cancers.
METHODS: HSP70/GPC3 peptides with high binding affinities for three HLA types (A*24:02, A*02:01, and A*02:06) were identified with our peptide prediction system. The peptides were intradermally administered with combined adjuvants on a weekly basis. This study was a phase I dose-escalation clinical trial, which was carried out in a three patients’ cohort; in total, 11 patients were enrolled for the recommended dose.
RESULTS: Seventeen patients received this vaccination therapy without dose-limiting toxicity. All treatment-related adverse events were of grades 1 to 2. Peptide-specific CTL induction by HSP70 and GPC3 proteins was observed in 11 (64.7%) and 13 (76.5%) cases, respectively, regardless of the HLA type. Serum tumor marker levels were decreased in 10 cases (58.8%). Immunological analysis using PBMCs indicated that patients receiving dose level 3 presented with significantly reduced T cell immunoglobulin and mucin-domain containing-3 (TIM3)-expressing CD4+ T cells after one course of treatment. PD-1 or TIM3-expressing CD4+ T cells and T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT)-expressing CD8+ T cells in PBMCs before vaccination were negative predictive factors for survival.
CONCLUSIONS: This novel peptide vaccination therapy was safe for patients with metastatic gastrointestinal cancers.
Reference: Cancer Immunology, Immunotherapy, (On-line Article)
Download: (https://link.springer.com/article/10.1007/s00262-020-02518-7)
YNP01 study:A phase I study of combination immunotherapy with HSP70 derived peptide, GPC3 derived peptide, IMP321 and Hiltonol for patients with advanced or metastatic solid cancer (PI: Hiroaki Nagano, MD, PhD, Professor and Chairman, Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University School of Medicine, Co-Investigator: Shoichi Hazama, MD, PhD, Professor, Department of Translational Research and Developmental Therapeutics against Cancer, Yamaguchi University School of Medicine, Collaboration: NEC Corporation, Cytlimic Inc.) (jRCTs061180058 (https://jrct.niph.go.jp/en-latest-detail/jRCTs061180058)

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