235P - Phase 1b study of nimotuzumab in combination with concurrent chemoradiotherapy in Japanese patients with locally advanced esophageal cancer

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Drug Development
Oesophageal Cancer
Presenter Takashi Ura
Citation Annals of Oncology (2016) 27 (suppl_9): ix68-ix85. 10.1093/annonc/mdw582
Authors T. Ura1, K. Kato2, W. Koizumi3, S. Iwasa2, C. Katada3, M. Azuma3, S. Ishikura4, Y. Nakao5, H. Onuma6, K. Muro1
  • 1Department Of Clinical Oncology, Aichi Cancer Center Hospital, 464-8681 - Nagoya/JP
  • 2Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 3Department Of Gastroenterology, Kitasato University School of Medicine, 252-0375 - Kanagawa/JP
  • 4Department Of Radiology, Koshigaya Municipal Hospital, 343-8577 - Saitama/JP
  • 5Pharmacovigilance Department, Daiichi Sankyo Co., Ltd, 103-8426 - Tokyo/JP
  • 6Oncology Clinical Development Department, Daiichi Sankyo Co., Ltd, 140-8710 - Tokyo/JP

Abstract

Background

Nimotuzumab is a recombinant humanized IgG1 monoclonal antibody directed against EGFR. The synergistic antitumor effect of nimotuzumab with radiotherapy has been demonstrated in patients (pts) with head and neck cancer and glioma. EGFR is highly expressed in esophageal cancer as head and neck cancer, and therefore high efficacy of nimotuzumab for esophageal cancer was expected. This study assessed the safety, tolerability, efficacy, and PK of nimotuzumab in combination with chemoradiotherapy in Japanese pts with esophageal cancer.

Methods

Japanese pts with stage II, III (excluding T4), and IV (only with supraclavicular lymph node) esophageal cancer, were enrolled. This was an open-label, dose-escalation study. Pts received nimotuzumab (level 1: 200 mg/week for 25 weeks, or level 2: 400 mg/week for first 10 weeks and 400 mg biweekly for next 15 weeks), combined with cisplatin (75 mg/m2 on day 1), and fluorouracil (1000 mg/m2 on days 1 to 4) every 4 weeks for 4 cycles. Radiotherapy was administered concurrently at the dose of 50.4 Gy. PK samples and tumor samples for additional biomarker study were also collected.

Results

A total of 10 pts were enrolled in level 1 (7 male, 3 female; median age 63 years, all pts were EGFR 3+ and with squamous cell carcinoma). Dose-limiting toxicities were observed in 2 pts (grade 3 infection and renal disorder) in level 1. An Independent Data Monitoring Committee judged it was acceptable to escalate to level 2; however, the sponsor of this study decided not to enroll any pts in level 2 because of a change in their development strategy. The common grade 3 or higher toxicities were lymphopenia (90%), leukopenia (60%), neutropenia (50%), and febrile neutropenia, decreased appetite, hyponatraemia, and radiation esophagitis (30% each). Neither treatment-related death nor grade 3 or higher skin toxicity was observed. Complete response rate was 50% (95% Cl, 16 – 84). Progression-free survival was 423 days (95% CI, 128 - 519). One- and 3-year survival rates were 80% (95% CI, 41 – 95) and 40% (95% CI, 12 - 67), respectively.

Conclusions

Nimotuzumab in combination with concurrent chemoradiotherapy was tolerable and effective for Japanese pts with esophageal cancer.

Clinical trial indentification

This study was registered with JapicCTI-101319, first released on 25 Oct 2010. The trial protocol number is DE766-A-J102.

Legal entity responsible for the study

Daiichi Sankyo Co., Ltd

Funding

Daiichi Sankyo Co., Ltd

Disclosure

T. Ura: Personal financial interests(Speaking):Merck Serono Co., Ltd, Ono Pharmaceutical Co., Ltd and Chugai Pharmaceutical Co., Ltd. K. Kato: Personal financial interests: Eli Lilly Japan. Institutional financial interests: Ono Pharmaceutical, Merckserono, MSD and Shionogi. W. Koizumi: Personal financial interests: Daiichi Sankyo Co., Ltd. S. Iwasa: Personal financial interests:DaiichiSankyo, EliLily JP, Chugai, MerckSerono, Otsuka. Institutional financial interests:DaiichiSankyo, EliLily JP, Chugai, MerckSerono, Ono, Taiho, AstraZeneca, Eisai, Astellas, Takeda, Bayer, Novartis, Yakult, MSD, Otsuka. Y. Nakao, H. Onuma: The employee of Daiichi Sankyo Co., Ltd. K. Muro: Personal financial interests(Speaking): Takeda, Chugai, Taiho, MerckSerono, Yakult and Eli Lilly. All other authors have declared no conflicts of interest.