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国立がん研究センター 東病院

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Department of Experimental Therapeutics

Toshihiko Doi, Yasutoshi Kuboki, Yoichi Naito, Kohei Shitara, Kenichi Harano, Junichiro Yuda, Shigehiro Koganemaru, Chikako Funasaka, Hiromichi Nakajima

Introduction

The NCC-EPOC Phase I Group was organized to promote early drug development, especially first in human (FIH) trials, and in 2012 the Phase I Group comprised two sub-units (NCCE-Kashiwa & NCC-Tsukiji) organized by each hospital. The goal of each of the units was to perform initial clinical evaluation of promising new anti-cancer compounds emerging from the laboratory. Our Phase 1 unit is the largest program in Japan - indeed in Asia - and we help develop new cancer drugs through early-phase trials.

In April 2013, the Department of Experimental Therapeutics was launched to strongly promote the EPOC missions as previously described. The members of the Department of Experimental Therapeutics comprised specialists in oncology fields. We also contributed to IITs using unapproved drugs and new academic seeds.

The Team and What We Do

Our team has conducted and managed early drug development, especially first in human (FIH) trials.

Research activities

This department is key to developing new anti-cancer drugs in our center as well as nationally, and while conducting FIH trials is the top priority, we also perform phase I trials. Recently, we joined the global phase I trial to accelerate new drug development in Japan. Video or teleconferences have been held with the EU and US sites, and we are discussing details of patient enrollment as well as further developmental strategy. Routine web-conferences are also held between Kashiwa and Tsukiji campuses every Friday morning, and we share information about adverse events and patient enrollment as well as referring candidates to each other to accelerate enrollment. Several IIT-FIH trials using new class seeds and also unapproved company agents are conducted by each unit.

Clinical trials

In 2024, 226 patients were enrolled in the phase I trial.

List of papers published

Journal

  1. Yuda J, Wang C, Terasawa T, Tajimi M, Osaga S, Miura M, et al. Treatment selection and influencing factors for chronic lymphocytic leukemia: a physician survey in Japan. Int J Clin Oncol 2025;30(1):157-67 doi 10.1007/s10147-024-02645-6.
  2. Koganemaru S, Fuchigami H, Morizono C, Shinohara H, Kuboki Y, Furuuchi K, et al. Potential Mechanisms of Interstitial Lung Disease Induced by Antibody-Drug Conjugates Based on Quantitative Analysis of Drug Distribution. Mol Cancer Ther 2025;24(2):242-50 doi 10.1158/1535-7163.MCT-24-0267.
  3. Shitara K, Yamaguchi K, Muro K, Yasui H, Sakai D, Oshima T, et al. Trastuzumab deruxtecan in patients with locally advanced or metastatic HER2-positive gastric cancer: a multicenter, open-label, expanded-access study. Int J Clin Oncol 2024;29(1):27-35 doi 10.1007/s10147-023-02422-x.
  4. Shitara K, Xu RH, Ajani JA, Moran D, Guerrero A, Li R, et al. Global prevalence of claudin 18 isoform 2 in tumors of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Gastric Cancer 2024;27(5):1058-68 doi 10.1007/s10120-024-01518-1.
  5. Shitara K, Shah MA, Lordick F, Van Cutsem E, Ilson DH, Klempner SJ, et al. Zolbetuximab in Gastric or Gastroesophageal Junction Adenocarcinoma. N Engl J Med 2024;391(12):1159-62 doi 10.1056/NEJMc2409512.
  6. Shitara K, Shah MA, Lordick F, Bang YJ, Ilson D, Van Cutsem E, et al. Zolbetuximab plus chemotherapy for locally advanced unresectable or metastatic stomach or gastroesophageal junction cancers: a plain language summary. Future Oncol 2024;20(26):1861-77 doi 10.1080/14796694.2024.2342107.
  7. Shitara K, Rha SY, Wyrwicz LS, Oshima T, Karaseva N, Osipov M, et al. Neoadjuvant and adjuvant pembrolizumab plus chemotherapy in locally advanced gastric or gastro-oesophageal cancer (KEYNOTE-585): an interim analysis of the multicentre, double-blind, randomised phase 3 study. Lancet Oncol 2024;25(2):212-24 doi 10.1016/S1470-2045(23)00541-7.
  8. Shitara K, Muro K, Watanabe J, Yamazaki K, Ohori H, Shiozawa M, et al. Baseline ctDNA gene alterations as a biomarker of survival after panitumumab and chemotherapy in metastatic colorectal cancer. Nat Med 2024;30(3):730-9 doi 10.1038/s41591-023-02791-w.
  9. Shitara K, Falcone A, Fakih MG, George B, Sundar R, Ranjan S, et al. Efficacy and Safety of Trifluridine/Tipiracil-Containing Combinations in Colorectal Cancer and Other Advanced Solid Tumors: A Systematic Review. Oncologist 2024;29(5):e601-e15 doi 10.1093/oncolo/oyae007.
  10. Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, et al. Trastuzumab deruxtecan in HER2-positive advanced gastric cancer: exploratory biomarker analysis of the randomized, phase 2 DESTINY-Gastric01 trial. Nat Med 2024;30(7):1933-42 doi 10.1038/s41591-024-02992-x.
  11. Shitara K. Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer: a plain language summary of the DESTINY-Gastric01 study. Future Oncol 2024;20(2):59-70 doi 10.2217/fon-2023-0245.
  12. Naito Y, Nakamura S, Kawaguchi-Sakita N, Ishida T, Nakayama T, Yamamoto Y, et al. Preliminary results from ASCENT-J02: a phase 1/2 study of sacituzumab govitecan in Japanese patients with advanced solid tumors. Int J Clin Oncol 2024;29(11):1684-95 doi 10.1007/s10147-024-02589-x.
  13. Kuboki Y, Koyama T, Matsubara N, Naito Y, Kondo S, Harano K, et al. PD-1 inhibition with retifanlimab and/or arginase inhibition with INCB001158 in Japanese patients with solid tumors: A phase I study. Cancer Med 2024;13(8):e6980 doi 10.1002/cam4.6980.
  14. Kuboki Y, Fakih M, Strickler J, Yaeger R, Masuishi T, Kim EJ, et al. Sotorasib with panitumumab in chemotherapy-refractory KRAS(G12C)-mutated colorectal cancer: a phase 1b trial. Nat Med 2024;30(1):265-70 doi 10.1038/s41591-023-02717-6.
  15. Koganemaru S, Fuchigami H, Yamashita H, Morizono C, Sunakawa H, Kawazoe A, et al. Quantitative Analysis of the Concentration of Trifluridine in Tumor Hypoxic Regions Using a Novel Platform Combining Functional Endoscopy and Mass Spectrometry. Clin Pharmacol Ther 2024;115(1):62-70 doi 10.1002/cpt.3066.
  16. Doi T, Yamamoto N, Ohkubo S. Pimitespib for the treatment of advanced gastrointestinal stromal tumors and other tumors. Future Oncol 2024;20(9):507-19 doi 10.2217/fon-2022-1172.
  17. Doi T, Takahashi S, Aoki D, Yonemori K, Hara H, Hasegawa K, et al. A first-in-human phase I study of TAS-117, an allosteric AKT inhibitor, in patients with advanced solid tumors. Cancer Chemother Pharmacol 2024;93(6):605-16 doi 10.1007/s00280-023-04631-7.
  18. Yuda J, Will C, Phillips DC, Abraham L, Alvey C, Avigdor A, et al. Selective MCL-1 inhibitor ABBV-467 is efficacious in tumor models but is associated with cardiac troponin increases in patients. Commun Med (Lond) 2023;3(1):154 doi 10.1038/s43856-023-00380-z.
  19. Yuda J, Doki N, Matsuoka H, Yokota T, Tomita A, Takahashi N, et al. Asciminib vs bosutinib in CML patients pretreated with >/=2 tyrosine kinase inhibitors: Results from the Japanese subgroup analysis of ASCEMBL study. Cancer Med 2023;12(3):2990-8 doi 10.1002/cam4.5212.
  20. Naito Y, Mishima S, Akagi K, Hayashi N, Hirasawa A, Hishiki T, et al. Japanese Society of Medical Oncology/Japan Society of Clinical Oncology/Japanese Society of Pediatric Hematology/Oncology-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors. Int J Clin Oncol 2023;28(7):827-40 doi 10.1007/s10147-023-02345-7.
  21. Kuboki Y, Terazawa T, Masuishi T, Nakamura M, Watanabe J, Ojima H, et al. Trifluridine/tipiracil+bevacizumab (BEV) vs. fluoropyrimidine-irinotecan+BEV as second-line therapy for metastatic colorectal cancer: a randomised noninferiority trial. Br J Cancer 2023;128(10):1897-905 doi 10.1038/s41416-023-02212-2.
  22. Koganemaru S, Kawai T, Fuchigami H, Maeda N, Koyama K, Kuboki Y, et al. Quantitative analysis of drug distribution in heterogeneous tissues using dual-stacking capillary electrophoresis-mass spectrometry. Br J Pharmacol 2023;180(6):762-74 doi 10.1111/bph.15988.
  23. Doi T, Shitara K, Kojima T, Kuboki Y, Matsubara N, Bando H, et al. Phase I study of the irreversible fibroblast growth factor receptor 1-4 inhibitor futibatinib in Japanese patients with advanced solid tumors. Cancer Sci 2023;114(2):574-85 doi 10.1111/cas.15486.
  24. Doi T, Matsubara N, Naito Y, Kuboki Y, Harano K, Ono M, et al. First-in-human study of E7130 (a tumor microenvironment-ameliorating microtubule inhibitor) in patients with advanced solid tumors: Primary results of the dose-escalation part. Cancer 2023;129(15):2348-59 doi 10.1002/cncr.34788.
  25. Naito Y, Sunami K, Kage H, Komine K, Amano T, Imai M, et al. Concordance Between Recommendations From Multidisciplinary Molecular Tumor Boards and Central Consensus for Cancer Treatment in Japan. JAMA Netw Open 2022;5(12):e2245081 doi 10.1001/jamanetworkopen.2022.45081.
  26. Kuboki Y, Shimizu T, Yonemori K, Kojima T, Kondo S, Koganemaru S, et al. Safety, Tolerability, and Pharmacokinetics of TAK-931, a Cell Division Cycle 7 Inhibitor, in Patients with Advanced Solid Tumors: A Phase I First-in-Human Study. Cancer Res Commun 2022;2(11):1426-35 doi 10.1158/2767-9764.CRC-22-0277.
  27. Doi T, Kuboki Y, Naito Y, Ishida M, Tanaka T, Takeuchi Y. A phase 1 trial of xentuzumab, an IGF-neutralizing antibody, in Japanese patients with advanced solid tumors. Cancer Sci 2022;113(3):1010-7 doi 10.1111/cas.15231.