409P - Updated results of phase 1 study of DS-8201a in patients with HER2 expressing non-breast, non-gastric malignancies

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Anti-Cancer Agents & Biologic Therapy
Drug Development
Presenter Junji Tsurutani
Citation Annals of Oncology (2017) 28 (suppl_5): v122-v141. 10.1093/annonc/mdx367
Authors J. Tsurutani1, T. Doi2, H. Iwata3, S. Takahashi4, S. Modi5, K. Tamura6, K. Shitara7, H. Taniguchi8, S. Taira9, B. Li10, A. Shimomura11, Y. Sato12, K. Akiyama12, Y. Fujisaki12, C. Lee13, A. Yver14, K. Nakagawa1
  • 1Depertment Of Oncology, Kindai University School of Medicine, 577-8502 - Osaka/JP
  • 2Department Of Experimental Therapeutics, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 3Breast Oncology, Aichi Cancer Center Hospital, 464-8681 - Nagoya/JP
  • 4Department Of Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 135-8550 - Tokyo/JP
  • 5Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 6Breast And Medical Oncology, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 7Gastroenterology And Gastrointestinal Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 8Department Of Clinical Oncology, Aichi Cancer Center Hospital, 464-8681 - Nagoya/JP
  • 9Department Of Medical Oncology, Cancer Institute Hospital of JFCR, 135-8550 - Tokyo/JP
  • 10Department Of Medicine, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 11Department Of Breast And Medical Oncology, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 12Oncology Clinical Development Department, DAIICHI SANKYO CO., LTD., 140-8710 - Tokyo/JP
  • 13Global Oncology R&d, Daiichi Sankyo, Inc., 08837 - Edison/US
  • 14Global Oncology R&d, Daiichi Sankyo Pharma Development, 8837 - Edison/US

Abstract

Background

DS-8201a is a HER2 targeting antibody-drug conjugate of high drug to antibody ratio (7 to 8) with a novel linker and topoisomerase I inhibitor. In preclinical studies, DS-8201a showed a broad antitumor spectrum, including efficacy against low HER2 expressing breast cancer (BC) and HER2 expressing non-gastric and non-breast cancers. The current phase 1 trial includes dose escalation (Part 1) and expansion (Part 2) including BC, gastric cancer (GC) and other HER2 expressing solid tumors.

Methods

Part 1 used a mCRM to identify the recommended dose in patients (pts) with BC or GC. Part 2 was designed to evaluate the safety and efficacy in 4 expansion cohorts: HER2 positive BC, HER2 positive GC, low HER2 expressing BC, and other solid tumors expressing HER2. HER2 expression was determined by IHC, FISH, NGS or other platforms. Adverse events (AEs), objective response rate (ORR), and disease control rate (DCR: CR + PR + SD) were assessed.

Results

Twenty four pts in Part 1 and 113 pts in Part 2 were enrolled. 24 of 113 pts were HER2 expressing solid tumors other than BC and GC. DS-8201a was administered up to 8.0 mg/kg in Part 1, and dose level of 6.4 mg/kg IV every 3 weeks was chosen. DLTs were not observed in the study. In the updated Part 1 results, confirmed ORR was 35%, DCR was 91% (BC: 88%, GC: 100%), and the median duration of treatment was ≥32 weeks in heavily pretreated BC and GC pts. Non-BC and non-GC cohort consists of 11 CRC, 5 NSCLC, 4 salivary gland, 2 Paget’s disease, 1 cholangiocarcinoma and 1 esophageal cancer. ORR including under confirmation and DCR were 33% and 91%, respectively in evaluable 12 pts. Two out of 5 evaluable pts with CRC and 2 out of 4 evaluable pts with salivary gland achieved PRs. Of all pts in this phase 1 study, the most common AEs of any grades were nausea (≥Gr1 60%; ≥Gr3 2%), decreased appetite (≥Gr1 55%; ≥Gr3 4%), vomiting (≥Gr1 30%; ≥Gr3 0%) and platelet count decreased (≥Gr1 30%; ≥Gr3 9%). Updated phase 1 results will be presented.

Conclusions

DS-8201a was well tolerated and is remarkably active in pts with heavily pretreated HER2 expressing BC and GC with durable disease control. Promising efficacy in HER2 expressing other tumors was observed and warrants further investigation.

Clinical trial identification

NCT02564900

Legal entity responsible for the study

Daiichi Sankyo CO., LTD.

Funding

Daiichi Sankyo CO., LTD.

Disclosure

J. Tsurutani: Paid honoraria directly by Eisai, Kyowa Hakko Kirin, Chugai, AstraZeneca, Novartis, Taiho. Paid for any consulting or advisory role by Novartis, Daiichi Sankyo, MSD, Lilly, Roche. Conducted research project funded by Daiich Sankyo, Roche, Lilly, MSD. T. Doi: Paid for consulting by Lilly, Chugai, Kyowa, Behringer, Novartis, MSD, Daiichi Sankyo, Amgen. Conducted study funded by Taiho, Novartis, Merck, Astellas, MSD, Janssen, Boehringer, Takeda, Pfizer, Lilly, Sumitomo, Chugai, Bayer, Kyowa, Daiichi Sankyo. H. Iwata: Paid honoraria directly by Daiichi Sankyo, Chugai, AstraZeneca. Paid for consulting or advisory role by Daiich Sankyo and Pfizer. Conducted research project funded by Daiich Sankyo, Chugai, AstraZeneca, Pfizer, Novartis, Eisai, MSD, Lilly. S. Takahashi: Paid honoraria directly by Eisai, Astellas, Taiho, Bayer, Daiichi Sankyo, Pfizer, AstraZeneca. Paid for consulting or advisory role by Chugai Astellas. Conducted study funded by Eisai, Chugai, MSD, Lilly, AstraZeneca, Novartis, Taiho, Daiichi Sankyo. K. Tamura: Conducted study funded by Daiichisankyo, MSD, pfizer, AstraZeneca. K. Shitara: Paid for consulting or advisory role by Chugai Pharma, Takeda, Bayer, Lilly, Bristol-Myers, Squibb. Conducted study funded by Dainippon Sumitomo Pharma, Lilly, MSD, Sanofi, Daiichi Sankyo, Taiho Pharmaceutical, Bayer, Chugai. H. Taniguchi: Honoraria for speaking or writing engagements from Takeda, Chugai, Merck Serono, Taiho, Bayer, Lilly, Yakult. Financial support for clinical trials or research found by Otsuka, Boehringer Ingelheim, MSD Oncology, Takeda. B. Li: Consulting and/or Advisory Board for Genentech, ThermoFisher Scientific, Biosceptre Australia. Principle Investigator of clinical trials supported by Genentech, AstraZeneca, BioMedValley. A. Shimomura: Conducted study funded by AstraZeneca. Y. Sato, K. Akiyama, Y. Fujisaki, C. Lee, A. Yver: Employee of Daiichi Sankyo. K. Nakagawa: Paid for any consulting or advisory role by Astellas. Ono, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo. Conducted study funded by GlaxoSmithKline, Yakult, AstraZeneca, PAREXEL, Kyowa Hakko, Otsuka, Pfizer, Astellas, Daiichi Sankyo. All other authors have declared no conflicts of interest.