Evaluating trastuzumab deruxtecan in patients with gastrooesophageal adenocarcinoma who are ctDNA and HER2 positive: DECIPHER

Operable gastrooesophageal adenocarcinoma (GOA) is treated with multimodality therapy which is curative in <50% of patients. Patients in the UK with operable GOA are treated with chemotherapy before and following surgery. Patients who have circulating tumour DNA (ctDNA) present after surgery have worse survival than ctDNA-negative patients. Trastuzumab deruxtecan (T-DXd), a novel human epidermal growth factor receptor 2 (HER2)-targeting antibody-drug conjugate is an effective drug in multiple tumour types and has been licensed to treat advanced HER2-positive GOA that has progressed after chemotherapy and trastuzumab and is European Society for Medical Oncology (ESMO) Guideline recommended. Evaluation of T-DXd in operable but micrometastatic GOA is an attractive option. DECIPHER is a multicentre, phase II trial testing the efficacy of T-DXd in reducing micrometastatic disease burden in HER2-positive GOA patients who are ctDNA positive after neoadjuvant chemotherapy and surgery. Patients will have their resection specimen and plasma analysed to confirm HER2 and ctDNA status post-operatively. Twenty-five ctDNA- and HER2-positive patients will be treated with 6.4 mg/kg T-DXd intravenously every 21 days for a maximum of eight cycles. Study follow-up visits will take place for a maximum of 2 years after treatment, with survival follow-up until the end of the study.