Title

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

Description

Gastrooesophageal (GOA) cancer is a common, global cancer. Those diagnosed early will generally have FLOT chemotherapy followed by surgery, followed by the same FLOT chemotherapy post-surgery.

Patients who are ctDNA positive (as confirmed by Natera’s Signatera assay) after chemotherapy and surgery are less likely to benefit from FLOT chemotherapy. Patients with pathologically documented GOA, with HER2 overexpression and who are ctDNA positive will be approached for DECIPHER.

DECIPHER aims to treat minimal residual disease in ctDNA patients with trastuzumab deruxtecan (T-DXd), a drug which has shown efficacy in advanced gastroesophageal adenocarcinoma, to reduce the chance of relapse. T-DXd is an antibody that targets HER2 cells. It attaches to the HER2 cells on the tumour and destroys them. All trial patients will be followed for up to 2 years to record their response to treatment.

DECIPHER aims to recruit 25 patients from 10-15 NHS Secondary Care Centres. Participants in the study will be treated with T-DXd at a dose of 6.4 mg/kg intravenously every 21 days for a maximum of 8 cycles. Treatment will cease when the patient either completes 8 cycles of treatment, disease recurrence, unacceptable toxicity, death or withdrawal from the study.

Objectives

Primary:

• To assess the efficacy of T-DXd in reducing micrometastatic disease burden in HER2 positive GOA patients who are ctDNA positive after chemotherapy and surgery.

Secondary:

• To assess the impact of T-DXd on ctDNA
• To assess the efficacy of T-DXd in prolonging time of macroscopic disease recurrence
• To assess the efficacy of T-DXd in prolonging survival
• To assess impact of T-DXd on symptoms and quality of life
• To assess the safety and tolerability of T-DXd

Tertiary:

• To assess the effect of T-DXd on ctDNA dynamics
• To assess the translational outcomes associated with sensitivity and resistance to T-DXd

Trial Design

A multicentre, open label, single stage, single arm A’Hern’s design.

Trial Status

Open to recruitment

Population

Patients with pathologically documented adenocarcinoma of the stomach (clinical stage before surgery of AJCC I-III), gastroesophageal junction, or oesophagus, with HER2 overexpression (IHC 3+ or IHC 2+/ISH+) based on local tissue testing results.

Funder

This trial is funded by Astra Zeneca