Abstract 500TiP
Background
Trastuzumab deruxtecan (T-DXd), an-ADC targeting HER2, is approved for treatment of patients with HER2-positive (IHC3+ or 2+/ISH-positive) metastatic gastroesophageal adenocarcinoma (mGEA). Notably, the exploratory analysis of the DESTINY-Gastric01 revealed the encouraging antitumor activity for HER2-low mGEA (confirmed ORR, 26.3% [IHC 2+/ISH−] and 9.5% [IHC 1+]). Given the greater intra-tumoral heterogeneity in HER2-low vs HER2-positive tumors, combinations with multiple chemotherapies might confer benefits for HER2-low tumor. Additionally, preclinical studies in mouse models have indicated that T-DXd activates dendritic cells and enhances MHC-I expression on tumor cells, suggesting synergistic effects with anti-PD1 therapy.
Trial design
EPOC2203 is a single-arm, phase Ib/II study to assess the efficacy and safety of T-DXd in combination with nivolumab and CAPOX as first-line for patients with HER2-low mGEA. The phase Ib part employs a conventional 3+3 design to determine the recommended phase II dose (RP2D). Patients received the T-DXd (5.4 mg/kg) in combination with nivolumab (360 mg/body) and CAPOX (capecitabine: 750 mg/m2 twice daily, days 1 – 14 and oxaliplatin: 70 mg/m2, day 1), every 3 weeks, at the initial dose level. The primary endpoint is DLT in phase Ib and ORR in phase II. Secondary endpoints include PFS, OS, DOR, DCR and safety. Hypothesis testing assumed a null ORR of 58% and an alternative ORR of 80% with a one-sided alpha of 0.1 and 0.8 power, respectively. The planned sample size is 28 patients treated with the RP2D. Enrollment began in November 2023. This trial is funded by Daiichi Sankyo and registered in Japan Registry of Clinical Trials (jRCT2031230477).
Clinical trial identification
This trial has been registered in Japan Registry of Clinical Trials (jRCT2031230477) from 25 November, 2023.
Legal entity responsible for the study
National Cancer Center Hospital East.
Funding
Daiichi Sankyo.
Disclosure
Y. Aoki: Financial Interests, Personal, Invited Speaker: Guardant Health Inc. H. Shoji: Financial Interests, Personal, Advisory Board: Ono Pharmaceutical Co., Ltd., Zymeworks inc.; Financial Interests, Institutional, Invited Speaker: Ono Pharmaceutical Co., Ltd., MSD, Astellas, Amgen, Daiichi Sankyo; Financial Interests, Institutional, Funding: Ono Pharmaceutical Co., Ltd., Takeda Pharmaceuticals. M. Furuta: Financial Interests, Personal, Invited Speaker: Eli Lilly, Bristol Myers Squibb, Merck & Co., Inc., Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. K. Minashi: Financial Interests, Institutional, Research Grant: Amgen, Taiho Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Astellas, Pharmaceutical Co., Ltd.,. H. Hara: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Boehringer Ingelheim, MSD; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, MSD, Ono, Bayer, Chugai, Lilly, Merck Biopharma, Taiho, Takeda, Yakult, Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Amgen, Astellas, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Dainippon Sumitomo, Janssen, Merck Biopharma, MSD, Ono, Taiho, ALX oncology. M. Wakabayashi: Financial Interests, Personal, Invited Speaker: Nihon Medi-Physics, Co., Ltd. A. Sato: Financial Interests, Personal, Invited Speaker: Astellas Pharma Inc.; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical, Boehringer Ingelheim, Bayer, Chugai Pharma, Eisai, MSD, Ono Pharmaceutical, Takeda, Dainippon Sumimoto Pharma, Oncolys Biopharma, Aspyerian Therapeutics, Pentax Medical Devices, Daiichi Sankyo/UCB Japan. N. Fuse: Financial Interests, Personal, Advisory Board: Astellas Pharma Inc. T. Kuwata: Financial Interests, Personal, Invited Speaker: MSD, Daiichi Sankyo, Astellas Pharma, Roche Diagnostics, Bayer, Falco Biosystems; Financial Interests, Personal, Advisory Board: Astellas Pharma; Financial Interests, Personal, Advisory Role: Roche Diagnostics, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Takeda. K. Shitara: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Takeda, Ono Pharmaceutical, MSD, Novartis, Daiichi Sankyo, Amgen, Guardant Health Japan Corp, Astellas Pharma Inc., Astellas, Bayer, AstraZeneca, Zymeworks Biopharmaceuticals Inc, ALX Oncology Inc; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Janssen, AstraZeneca, Eli Lilly, Astellas, Ono Pharmaceutical; Financial Interests, Institutional, Research Grant: Astellas, Ono Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, Chugai Pharmaceutical, MSD, Eisai, Amgen, PRA Health Sciences. All other authors have declared no conflicts of interest.