Abstract 1260TiP
Background
Despite promising results following implementation of neoadjuvant chemoradiation (nCRT) prior to surgery in resectable esophageal adenocarcinoma (EAC) (van Hagen et al., NEJM, 2012) and the introduction of adjuvant nivolumab in case of incomplete response (Kelly et al., NEJM, 2021), prognosis remains dismal. Many patients eventually develop metastatic disease, and there is an unmet need to improve current therapies. In 15% to 43% of EAC cases, overexpression and/or gene amplification of the human epidermal growth factor receptor 2 (HER2) is observed. The HER2 receptor activates downstream signaling pathways involved in cell survival, proliferation and invasion, qualifying HER2 as a target for therapy. HER2 receptor signaling can be blocked with trastuzumab and pertuzumab, resulting in tumor inhibition by preventing ligand binding and stimulating receptor degradation. Stroes et al. (2019) showed that addition of trastuzumab and pertuzumab to nCRT was feasible and demonstrated promising activity. In this phase III study, we investigate if the addition of trastuzumab and pertuzumab to nCRT improves overall survival of HER2-positive EAC patients.
Trial design
TRAP-2 is a multi-center, randomized, open-label phase III clinical trial in patients with HER2-positive, surgically resectable adenocarcinoma of the esophagus or gastroesophageal junction (NCT05188313). To assess efficacy of HER2 inhibition in addition to nCRT, 388 patients will be randomized in a 1:1 ratio to receive nCRT with or without trastuzumab (4 mg/kg on day 1, 2 mg/kg weekly in weeks 2 to 6, and 6 mg/kg weekly in weeks 7, 10, and 13) and pertuzumab (840 mg every 3 weeks). The primary endpoint is overall survival. Secondary endpoints are progression-free survival, pathological response to nCRT, R0 resection rates, safety, and quality of life. Additionally, using NanoString expression profiling and systemic immune profiling, the presence of predictive biomarkers in tumor tissue and blood-derived samples will be analyzed to predict treatment response. The study is open for inclusion and ongoing.
Clinical trial identification
NCT05188313.
Editorial acknowledgement
Legal entity responsible for the study
Amsterdam University Medical Centers, location Academic Medical Center.
Funding
Zorg Instituut Nederland.
Disclosure
M.I. van Berge Henegouwen: Non-Financial Interests, Institutional, Advisory Role: Medtronic, Johnson & Johnson, Mylan, Alesi Surgical; Financial Interests, Institutional, Sponsor/Funding: Olympus, Stryker. N. Haj Mohammad: Non-Financial Interests, Institutional, Advisory Role: Eli Lilly, Servier, MSD, BMS, AstraZeneca. M.F. Bijlsma: Non-Financial Interests, Institutional, Advisory Role: Servier; Financial Interests, Institutional, Sponsor/Funding: Celgene, LEAD Pharma. H.W.M. van Laarhoven: Financial Interests, Institutional, Advisory Board: BMS, MSD; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: Nordic Pharma, Servier; Financial Interests, Institutional, Research Grant, REPEAT study: Bayer; Financial Interests, Institutional, Research Grant: BMS, Philips; Financial Interests, Institutional, Invited Speaker, FRACTION study: BMS; Financial Interests, Institutional, Research Grant, ACTION study: Celgene; Financial Interests, Institutional, Research Grant, DECO study: Janssen; Financial Interests, Institutional, Invited Speaker, RAINFALL study: Lilly; Financial Interests, Institutional, Invited Speaker, KEYNOTE 062 and KEYNOTE 181 study: Merck/MSD; Financial Interests, Institutional, Research Grant, SOX study: Nordic Pharma; Financial Interests, Institutional, Research Grant, TRAP study, PERFECT study; local PI of JACOB study: Roche; Financial Interests, Institutional, Research Grant, LyRICX study: Servier; Financial Interests, Institutional, Research Grant, TAPESTRY study: Merck; Financial Interests, Institutional, Research Grant, Research money and investigational product: Incyte; Non-Financial Interests, Institutional, Product Samples, For all clinical study mentioned, study medication is provided: See 'research funding'. All other authors have declared no conflicts of interest.