A single arm phase II trial of trastuzumab deruxtecan in patients with gastrooesophageal adenocarcinoma cancer who are ctDNA and HER2 positive: DECIPHER.

Abstract

TPS512 Background: Oesophagogastric adenocarcinoma (OGA) is globally prevalent and frequently advanced at presentation. Less than 50% of patients with operable OGA are cured when treated with multimodality therapy. Patients in the UK with operable OGA, are treated with FLOT prior to and following surgery. However, patients who have circulating tumour DNA (ctDNA) in their blood after surgery have worse survival than ctDNA negative patients. Therefore, use of novel treatment approaches aiming to cure this micrometastatic disease are considered a rational and appropriate treatment approach. Trastuzumab deruxtecan (T-DXd), a novel HER2-targeting antibody drug conjugate, is licensed to treat advanced, previously treated HER2 positive OGA. Therefore, there is a need to evaluate T-DXd in resectable HER2 and ctDNA positive OGA, where options are limited. Methods: Co-ordinated by the Cancer Research UK Southampton Clinical Trials Unit, DECIPHER is a single arm, multicentre, phase II trial testing the effect of T-DXd on reducing micrometastatic disease burden in HER2 positive OGA patients who are ctDNA positive after chemotherapy and surgery. To be eligible, participants must have been treated with chemotherapy before surgery for at least 6 weeks and must have recovered from surgery with no evidence of metastatic disease on post-surgical imaging. HER2 positive patients are recruited to the tissue testing stage of the trial prior to surgery. Patients who are ctDNA positive after surgery will be treated with T-DXd at a dose of 6.4 mg/kg intravenously every 21 days for a maximum of 8 cycles or until disease recurrence. If required, patients may dose reduce, but no dose re-escalation will be permitted. A clinically validated, personalised, tumour-informed ctDNA assay (signatera, Natera, Inc.) will be utilised to detect ctDNA in patient plasma samples. The primary endpoint is the percentage of patients who are ctDNA negative after 4 cycles of treatment. Secondary endpoints include ctDNA clearance after each cycle, disease free survival, overall survival, quality of life and frequency of adverse events. DECIPHER (NCT05965479) opened in April 2024 and will run in approximately 15 UK secondary care hospitals with the aim of recruiting 25 evaluable patients (recruitment to the tissue testing stage is currently 27 on 23-Sep-2024). Clinical trial information: NCT05965479 .