Annual Report 2020

Department of Experimental Therapeutics

Noboru Yamamoto, Toshio Shimizu, Kan Yonemori, Satoru Iwasa, Shunsuke Kondo, Tatsuya Yoshida, Kazuki Sudo, Takafumi Koyama, Yuki Katsuya, Makoto Nishino

Introduction

 In April 2015, the affiliation of the Department of Experimental Therapeutics was updated from the NCC-EPOC (cf. the Exploratory Oncology Research & Clinical Trial Center) to the NCC-Hospital. The goal of this department is to perform initial clinical evaluations of promising new anti-cancer compounds emerging from the laboratory in phase I trials. The staff consists of specialists from various oncology fields (i.e., thoracic oncology, breast and medical oncology, gastro-intestinal oncology, hepato-biliary and pancreatic oncology, and immuno-oncology).

The Team and What We Do

 This department plays a key role in new anti-cancer drug development in Japan and other countries in Asia. Our top priority is to conduct FIH trials, but we also perform phase I trials for solid tumors (i.e., all comers). We recently joined the global phase I trials to accelerate the new drug development in Japan. We hold web conferences and teleconferences with EU and US sites, and discuss patient enrollment and further developmental strategies. Routine web conferences are also held between the NCC-Hospital (Tokyo) and the NCC-East hospital (Chiba) every Friday morning, and we share information on adverse events and patient enrollment and refer the candidates to each other to accelerate enrollment. Currently, most of the phase I trials in Japan (i.e., first in Japan phase I trials, first in human trials) are conducted at the NCC-Hospital and NCC-East hospital with close collaboration.

Research activities

 Elucidating the proof of concept (POC) is essential in new anti-cancer drug development especially in early phases. We therefore conduct several translational research (TR) projects in collaboration with research institutes. We are also conducting TR with the pharmaceutical industry to discover new targets for anti-immune therapy using human tissue (tumor and normal tissue) samples. To facilitate the POC analyses in phase I trials, a phase I biobank study was launched in 2018.

Clinical trials

 In fiscal 2020, 86 phase I trials including 40 FIH trials were conducted.

Education

 In 2020, the 2nd NCCH & RI Tsukiji TR Board activity Web was held on October 21 at the NCC-Tsukiji campus.

List of papers published in 2020

Journal

1. Kitadai R, Shimoi T, Sudo K, Noguchi E, Nagata Y, Sawada R, Takashima A, Boku N, Yonemori K. Efficacy of second-line treatment and prognostic factors in patients with advanced malignant peritoneal mesothelioma: a retrospective study. BMC Cancer, 21:294, 2021

2. Shirasawa M, Yoshida T, Horinouchi H, Kitano S, Arakawa S, Matsumoto Y, Shinno Y, Okuma Y, Goto Y, Kanda S, Watanabe R, Yamamoto N, Watanabe SI, Ohe Y, Motoi N. Prognostic impact of peripheral blood neutrophil to lymphocyte ratio in advanced-stage pulmonary large cell neuroendocrine carcinoma and its association with the immune-related tumour microenvironment. Br J Cancer, 124:925-932, 2021

3. Shirasawa M, Yoshida T, Takayanagi D, Shiraishi K, Yagishita S, Sekine K, Kanda S, Matsumoto Y, Masuda K, Shinno Y, Okuma Y, Goto Y, Horinouchi H, Hamada A, Kohno T, Yamamoto N, Watanabe SI, Ohe Y, Motoi N. Activity and Immune Correlates of Programmed Death-1 Blockade Therapy in Patients With Advanced Large Cell Neuroendocrine Carcinoma. Clin Lung Cancer, 2021

4. Takeyasu Y, Yoshida T, Shibaki R, Matsumoto Y, Goto Y, Kanda S, Horinouchi H, Yamamoto N, Motoi N, Ohe Y. Differential Efficacy of Pembrolizumab According to Metastatic Sites in Patients With PD-L1 Strongly Positive (TPS ≧ 50%) NSCLC. Clin Lung Cancer, 22:127-133.e3, 2021

5. Masuda K, Horinouchi H, Tanaka M, Higashiyama R, Shinno Y, Sato J, Matsumoto Y, Okuma Y, Yoshida T, Goto Y, Yamamoto N, Ohe Y. Efficacy of anti-PD-1 antibodies in NSCLC patients with an EGFR mutation and high PD-L1 expression. J Cancer Res Clin Oncol, 147:245-251, 2021

6. Fukahori M, Kato K, Taniguchi H, Ohtomo R, Takahashi N, Shoji H, Iwasa S, Honma Y, Takashima A, Hamaguchi T, Yamada Y, Shimada Y, Ito Y, Itami J, Hokamura N, Igaki H, Tachimori Y, Miwa K, Torimura T, Boku N. Relationship between cervical esophageal squamous cell carcinoma and human papilloma virus infection and gene mutations. Mol Clin Oncol, 14:41, 2021

7. Ikeda M, Okusaka T, Ohno I, Mitsunaga S, Kondo S, Ueno H, Morizane C, Gemmoto K, Suna H, Ushida Y, Furuse J. Phase I studies of peptide vaccine cocktails derived from GPC3, WDRPUH and NEIL3 for advanced hepatocellular carcinoma. Immunotherapy, 13:371-385, 2021

8. Arakawa A, Ichikawa H, Kubo T, Motoi N, Kumamoto T, Nakajima M, Yonemori K, Noguchi E, Sunami K, Shiraishi K, Kakishima H, Yoshida H, Hishiki T, Kawakubo N, Kuroda T, Kiyokawa T, Yamada K, Yanaihara N, Takahashi K, Okamoto A, Hirabayashi S, Hasegawa D, Manabe A, Ono K, Matsuoka M, Arai Y, Togashi Y, Shibata T, Nishikawa H, Aoki K, Yamamoto N, Kohno T, Ogawa C. Vaginal Transmission of Cancer from Mothers with Cervical Cancer to Infants. N Engl J Med, 384:42-50, 2021

9. Doi T, Fujiwara Y, Shitara K, Shimizu T, Yonemori K, Matsubara N, Ohno I, Kogawa T, Naito Y, Leopold L, Munteanu M, Yatsuzuka N, Han SR, Samkari A, Yamamoto N. The safety and tolerability of epacadostat alone and in combination with pembrolizumab in patients with advanced solid tumors: results from a first-in-Japanese phase I study (KEYNOTE-434). Invest New Drugs, 39:152-162, 2021

10. Fujiwara Y, Kenmotsu H, Yamamoto N, Shimizu T, Yonemori K, Ocampo C, Parikh A, Okubo S, Fukasawa K, Murakami H. Phase 1 study of telisotuzumab vedotin in Japanese patients with advanced solid tumors. Cancer Med, 10:2350-2358, 2021

11. Harding JJ, Moreno V, Bang YJ, Hong MH, Patnaik A, Trigo J, Szpurka AM, Yamamoto N, Doi T, Fu S, Calderon B, Velez de Mendizabal N, Calvo E, Yu D, Gandhi L, Liu ZT, Galvao VR, Leow CC, de Miguel MJ. Blocking TIM-3 in Treatment-refractory Advanced Solid Tumors: A Phase Ia/b Study of LY3321367 with or without an Anti-PD-L1 Antibody. Clin Cancer Res, 27:2168-2178, 2021

12. Hellmann MD, Bivi N, Calderon B, Shimizu T, Delafontaine B, Liu ZT, Szpurka AM, Copeland V, Hodi FS, Rottey S, Aftimos P, Piao Y, Gandhi L, Galvao VR, Leow CC, Doi T. Safety and Immunogenicity of LY3415244, a Bispecific Antibody Against TIM-3 and PD-L1, in Patients With Advanced Solid Tumors. Clin Cancer Res, 27:2773-2781, 2021

13. Kitano S, Shimizu T, Koyama T, Ebata T, Iwasa S, Kondo S, Shimomura A, Fujiwara Y, Yamamoto N, Paccaly A, Li S, Rietschel P, Sims T. Dose exploration results from Phase 1 study of cemiplimab, a human monoclonal programmed death (PD)-1 antibody, in Japanese patients with advanced malignancies. Cancer Chemother Pharmacol, 87:53-64, 2021

14. Kondo S, Shimizu T, Koyama T, Sato J, Iwasa S, Yonemori K, Fujiwara Y, Shimomura A, Kitano S, Tamura K, Yamamoto N. First-in-human study of the cancer peptide vaccine TAS0313 in patients with advanced solid tumors. Cancer Sci, 112:1514-1523, 2021

15. Kudo M, Tsuchiya K, Kato N, Hagihara A, Numata K, Aikata H, Inaba Y, Kondo S, Motomura K, Furuse J, Ikeda M, Morimoto M, Achira M, Kuroda S, Kimura A. Cabozantinib in Japanese patients with advanced hepatocellular carcinoma: a phase 2 multicenter study. J Gastroenterol, 56:181-190, 2021

16. Lala M, Li TR, de Alwis DP, Sinha V, Mayawala K, Li M, Yamamoto N, Siu LL, Chartash E, Aboshady H, Jain L. Corrigendum to "A six-weekly (Q6W) dosing schedule for pembrolizumab in patients with cancer based on evaluation using modelling and simulation" [Eur J Canc 131 (2020) 68-75]. Eur J Cancer, 144:400, 2021

17. Ono A, Murakami H, Seto T, Shimizu T, Watanabe S, Takeshita S, Takeda K, Toyoshima J, Nagase I, Bahceci E, Morishita M, Morita S, Fukuoka M, Nakagawa K. Safety and Antitumor Activity of Repeated ASP3026 Administration in Japanese Patients with Solid Tumors: A Phase I Study. Drugs R D, 21:65-78, 2021

18. Powderly J, Spira A, Kondo S, Doi T, Luke JJ, Rasco D, Gao B, Tanner M, Cassier PA, Gazzah A, Italiano A, Tosi D, Afar DE, Parikh A, Engelhardt B, Englert S, Lambert SL, Kasichayanula S, Mensing S, Menon R, Vosganian G, Tolcher A. Model Informed Dosing Regimen and Phase I Results of the Anti-PD-1 Antibody Budigalimab (ABBV-181). Clin Transl Sci, 14:277-287, 2021

19. Shimizu T, Kim DW, Loong HH, Lin CC, Ng MC, Yamamoto N, Ma B, Tan DS. Overcoming the impact of the COVID-19 pandemic on oncology early phase trials and drug development in Asia-Experiences and perspectives of the Asian Oncology Early Phase 1 Consortium. Asia Pac J Clin Oncol, 2021

20. Sunami K, Naito Y, Aimono E, Amano T, Ennishi D, Kage H, Kanai M, Komine K, Koyama T, Maeda T, Morita S, Sakai D, Kohsaka S, Tsuchihara K, Yoshino T. The initial assessment of expert panel performance in core hospitals for cancer genomic medicine in Japan. Int J Clin Oncol, 26:443-449, 2021

21. Takahashi S, Fujiwara Y, Nakano K, Shimizu T, Tomomatsu J, Koyama T, Ogura M, Tachibana M, Kakurai Y, Yamashita T, Sakajiri S, Yamamoto N. Safety and pharmacokinetics of milademetan, a MDM2 inhibitor, in Japanese patients with solid tumors: A phase I study. Cancer Sci, 112:2361-2370, 2021

22. Yamamoto N, Shimizu T, Yonemori K, Kitano S, Kondo S, Iwasa S, Koyama T, Sudo K, Sato J, Tamura K, Tomomatsu J, Ono M, Fukuda N, Takahashi S. A first-in-human, phase 1 study of the NEDD8 activating enzyme E1 inhibitor TAS4464 in patients with advanced solid tumors. Invest New Drugs, 2021

23. Yoh K, Seto T, Satouchi M, Nishio M, Yamamoto N, Murakami H, Nogami N, Nosaki K, Kohno T, Tsuta K, Nomura S, Ikeno T, Wakabayashi M, Sato A, Matsumoto S, Goto K. Final survival results for the LURET phase II study of vandetanib in previously treated patients with RET-rearranged advanced non-small cell lung cancer. Lung Cancer, 155:40-45, 2021

24. Yonemori K, Shimizu T, Kondo S, Iwasa S, Koyama T, Kitano S, Sato J, Shimomura A, Shibaki R, Suri A, Kase Y, Sumino S, Tamura K, Yamamoto N. The safety, tolerability and pharmacokinetics of niraparib in Japanese patients with solid tumours: results of a phase I dose-escalation study. Jpn J Clin Oncol, 51:693-699, 2021

25. Ryu S, Ohuchi M, Yagishita S, Shimoi T, Yonemori K, Tamura K, Fujiwara Y, Hamada A. Visualization of the distribution of nanoparticle-formulated AZD2811 in mouse tumor model using matrix-assisted laser desorption ionization mass spectrometry imaging. Sci Rep, 10:15535, 2020

26. Watanuki R, Shimomura A, Yazaki S, Noda-Narita S, Sumiyoshi-Okuma H, Nishikawa T, Tanioka M, Sudo K, Shimoi T, Noguchi E, Yonemori K, Tamura K. Survival outcomes in patients with human epidermal growth factor receptor 2 positive metastatic breast cancer administered a therapy following trastuzumab emtansine treatment. Medicine (Baltimore), 99:e22331, 2020

27. Shirasawa M, Yoshida T, Matsumoto Y, Shinno Y, Okuma Y, Goto Y, Horinouchi H, Yamamoto N, Watanabe SI, Ohe Y, Motoi N. Impact of chemoradiotherapy on the immune-related tumour microenvironment and efficacy of anti-PD-(L)1 therapy for recurrences after chemoradiotherapy in patients with unresectable locally advanced non-small cell lung cancer. Eur J Cancer, 140:28-36, 2020

28. Watanabe S, Shimomura A, Kubo T, Sekimizu M, Seo T, Watanabe SI, Kawai A, Yamamoto N, Tamura K, Kohno T, Ichikawa H, Yoshida A. BRAF V600E mutation is a potential therapeutic target for a small subset of synovial sarcoma. Mod Pathol, 33:1660-1668, 2020

29. Hosoba R, Makita S, Shiotsuka M, Kobayashi O, Nakano K, Muroya M, Okada N, Suzuki M, Ida H, Fukuhara S, Munakata W, Suzuki T, Maruyama D, Maeshima AM, Matsushita H, Yamamoto N, Ohe Y, Iwata S, Izutsu K. COVID-19 pneumonia in a patient with adult T-cell leukemia-lymphoma. J Clin Exp Hematop, 60:174-178, 2020

30. Murakami S, Shibaki R, Matsumoto Y, Yoshida T, Goto Y, Kanda S, Horinouchi H, Fujiwara Y, Yamamoto N, Ohe Y. Association between serum level soluble programmed cell death ligand 1 and prognosis in patients with non-small cell lung cancer treated with anti-PD-1 antibody. Thorac Cancer, 11:3585-3595, 2020

31. Okuma Y, Goto Y, Ohyanagi F, Sunami K, Nakahara Y, Kitazono S, Kudo K, Tambo Y, Kanda S, Yanagitani N, Horiike A, Horinouchi H, Fujiwara Y, Nokihara H, Yamamoto N, Nishio M, Ohe Y, Hosomi Y. Phase II trial of S-1 treatment as palliative-intent chemotherapy for previously treated advanced thymic carcinoma. Cancer Med, 9:7418-7427, 2020

32. Sato J, Satouchi M, Itoh S, Okuma Y, Niho S, Mizugaki H, Murakami H, Fujisaka Y, Kozuki T, Nakamura K, Nagasaka Y, Kawasaki M, Yamada T, Machida R, Kuchiba A, Ohe Y, Yamamoto N. Lenvatinib in patients with advanced or metastatic thymic carcinoma (REMORA): a multicentre, phase 2 trial. Lancet Oncol, 21:843-850, 2020

33. Kanda S, Ohe Y, Goto Y, Horinouchi H, Fujiwara Y, Nokihara H, Yamamoto N, Yamamoto T, Tamura T. Five-year safety and efficacy data from a phase Ib study of nivolumab and chemotherapy in advanced non-small-cell lung cancer. Cancer Sci, 111:1933-1942, 2020

34. Sato J, Kitano S, Motoi N, Ino Y, Yamamoto N, Watanabe S, Ohe Y, Hiraoka N. CD20+ tumor-infiltrating immune cells and CD204+ M2 macrophages are associated with prognosis in thymic carcinoma. Cancer Sci, 111:1921-1932, 2020

35. Mizuno T, Horinouchi H, Watanabe S, Sato J, Morita R, Murakami S, Goto Y, Kanda S, Fujiwara Y, Yamamoto N, Ohe Y. Number of metastatic organs negatively affects the treatment sequence in patients with EGFR-TKI failure. Thorac Cancer, 11:1038-1044, 2020

36. Otsuka R, Iwasa S, Yanai T, Hirano H, Shoji H, Honma Y, Okita N, Takashima A, Kato K, Hashimoto H, Sekiguchi M, Makino Y, Boku N, Yamaguchi M. Impact of peripheral neuropathy induced by platinum in first-line chemotherapy on second-line chemotherapy with paclitaxel for advanced gastric cancer. Int J Clin Oncol, 25:595-601, 2020

37. Nagata Y, Kato K, Miyamoto T, Hirano H, Shoji H, Iwasa S, Honma Y, Takashima A, Hamaguchi T, Matsushita H, Nagashima K, Saruta M, Boku N. Safety and efficacy of cell-free and concentrated ascites reinfusion therapy (CART) in gastrointestinal cancer patients with massive ascites treated with systemic chemotherapy. Support Care Cancer, 28:5861-5869, 2020

38. Kato K, Doki Y, Ura T, Hamamoto Y, Kojima T, Tsushima T, Hironaka S, Hara H, Kudo T, Iwasa S, Muro K, Yasui H, Minashi K, Yamaguchi K, Ohtsu A, Kitagawa Y. Long-term efficacy and predictive correlates of response to nivolumab in Japanese patients with esophageal cancer. Cancer Sci, 111:1676-1684, 2020

39. Iwasa S, Kudo T, Takahari D, Hara H, Kato K, Satoh T. Correction to: Practical guidance for the evaluation of disease progression and the decision to change treatment in patients with advanced gastric cancer receiving chemotherapy. Int J Clin Oncol, 25:1233, 2020

40. Nakatani Y, Kato K, Shoji H, Iwasa S, Honma Y, Takashima A, Ushijima T, Ito Y, Itami J, Boku N. Comparison of involved field radiotherapy and elective nodal irradiation in combination with concurrent chemotherapy for T1bN0M0 esophageal cancer. Int J Clin Oncol, 25:1098-1104, 2020

41. Tamura N, Honma Y, Sekine S, Tsukamoto S, Hirano H, Okita N, Shoji H, Iwasa S, Takashima A, Kato K, Boku N. Case report: potential treatment of metastatic amphicrine carcinoma of the rectum with FOLFOXIRI chemotherapy. Oxf Med Case Reports, 2020:omaa097, 2020

42. Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med, 382:2419-2430, 2020

43. Yoo C, Oh DY, Choi HJ, Kudo M, Ueno M, Kondo S, Chen LT, Osada M, Helwig C, Dussault I, Ikeda M. Phase I study of bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with pretreated biliary tract cancer. J Immunother Cancer, 8:2020

44. Ebata T, Shimizu T, Fujiwara Y, Tamura K, Kondo S, Iwasa S, Yonemori K, Shimomura A, Kitano S, Koyama T, Sato N, Nakai K, Inatani M, Yamamoto N. Phase I study of the indoleamine 2,3-dioxygenase 1 inhibitor navoximod (GDC-0919) as monotherapy and in combination with the PD-L1 inhibitor atezolizumab in Japanese patients with advanced solid tumours. Invest New Drugs, 38:468-477, 2020

45. Fujiwara Y, Kuchiba A, Koyama T, Machida R, Shimomura A, Kitano S, Shimizu T, Yamamoto N. Infection risk with PI3K-AKT-mTOR pathway inhibitors and immune checkpoint inhibitors in patients with advanced solid tumours in phase I clinical trials. ESMO Open, 5:2020

46. Kang YK, Bang YJ, Kondo S, Chung HC, Muro K, Dussault I, Helwig C, Osada M, Doi T. Safety and Tolerability of Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGFβ and PD-L1, in Asian Patients with Pretreated Recurrent or Refractory Gastric Cancer. Clin Cancer Res, 26:3202-3210, 2020

47. Kondo S, Tajimi M, Funai T, Inoue K, Asou H, Ranka VK, Wacheck V, Doi T. Phase 1 dose-escalation study of a novel oral PI3K/mTOR dual inhibitor, LY3023414, in patients with cancer. Invest New Drugs, 38:1836-1845, 2020

48. Koyama T, Shimizu T, Iwasa S, Fujiwara Y, Kondo S, Kitano S, Yonemori K, Shimomura A, Iizumi S, Sasaki T, Furuse J, Yamamoto N. First-in-human phase I study of E7090, a novel selective fibroblast growth factor receptor inhibitor, in patients with advanced solid tumors. Cancer Sci, 111:571-579, 2020

49. Niho S, Yoshida T, Akimoto T, Sakamaki K, Ono A, Seto T, Nishio M, Yamamoto N, Hida T, Okamoto H, Kurata T, Satouchi M, Goto K, Yamanaka T, Ohe Y. Randomized phase II study of chemoradiotherapy with cisplatin + S-1 versus cisplatin + pemetrexed for locally advanced non-squamous non-small cell lung cancer: SPECTRA study. Lung Cancer, 141:64-71, 2020

50. Nishio M, Kato T, Niho S, Yamamoto N, Takahashi T, Nogami N, Kaneda H, Fujita Y, Wilner K, Yoshida M, Isozaki M, Wada S, Tsuji F, Nakagawa K. Safety and efficacy of first-line dacomitinib in Japanese patients with advanced non-small cell lung cancer. Cancer Sci, 111:1724-1738, 2020

51. Okuma HS, Yonemori K, Narita SN, Sukigara T, Hirakawa A, Shimizu T, Shibata T, Kawai A, Yamamoto N, Nakamura K, Nishida T, Fujiwara Y. MASTER KEY Project: Powering Clinical Development for Rare Cancers Through a Platform Trial. Clin Pharmacol Ther, 108:596-605, 2020

52. Gill K, Happel AU, Pidwell T, Mendelsohn A, Duyver M, Johnson L, Meyer L, Slack C, Strode A, Mendel E, Fynn L, Wallace M, Spiegel H, Jaspan H, Passmore JA, Hosek S, Smit D, Rinehart A, Bekker LG. An open-label, randomized crossover study to evaluate the acceptability and preference for contraceptive options in female adolescents, 15 to 19 years of age in Cape Town, as a proxy for HIV prevention methods (UChoose). J Int AIDS Soc, 23:e25626, 2020

53. Satomi-Tsushita N, Honma Y, Nagashima K, Ito Y, Hirano H, Shoji H, Takashima A, Iwasa S, Kato K, Hamaguchi T, Itami J, Boku N. Risk Factors of Severe Benign Cicatricial Stricture After Definitive Chemoradiation for Localized T3 Esophageal Carcinoma. Anticancer Res, 40:1071-1077, 2020

54. Shibaki R, Murakami S, Matsumoto Y, Yoshida T, Goto Y, Kanda S, Horinouchi H, Fujiwara Y, Yamamoto N, Kusumoto M, Yamamoto N, Ohe Y. Association of immune-related pneumonitis with the presence of preexisting interstitial lung disease in patients with non-small lung cancer receiving anti-programmed cell death 1 antibody. Cancer Immunol Immunother, 69:15-22, 2020

55. Shimizu T, Nishio K, Sakai K, Okamoto I, Okamoto K, Takeda M, Morishita M, Nakagawa K. Phase I safety and pharmacokinetic study of YM155, a potent selective survivin inhibitor, in combination with erlotinib in patients with EGFR TKI refractory advanced non-small cell lung cancer. Cancer Chemother Pharmacol, 86:211-219, 2020

56. Sudo K, Kato K, Matsuzaki J, Takizawa S, Aoki Y, Shoji H, Iwasa S, Honma Y, Takashima A, Sakamoto H, Naka T, Sekine S, Boku N, Ochiya T. Identification of serum microRNAs predicting the response of esophageal squamous-cell carcinoma to nivolumab. Jpn J Clin Oncol, 50:114-121, 2020

57. Tamura N, Fujiwara Y, Hashimoto T, Shiraishi H, Kitano S, Shimizu T, Kuwano K, Yamamoto N, Motoi N. Correlation between the expression of folate receptor alpha (FRα) and clinicopathological features in patients with lung adenocarcinoma. Lung Cancer, 145:152-157, 2020

58. Yamamoto N, Ryoo BY, Keam B, Kudo M, Lin CC, Kunieda F, Ball HA, Moran D, Komatsu K, Takeda K, Fukuda M, Furuse J, Morita S, Doi T. A phase 1 study of oral ASP5878, a selective small-molecule inhibitor of fibroblast growth factor receptors 1-4, as a single dose and multiple doses in patients with solid malignancies. Invest New Drugs, 38:445-456, 2020