NCT05504720

Evaluating Pembrolizumab, Trastuzumab and FLOT as Perioperative Treatment of HER2-positive, Localized Esophagogastric Adenocarcinoma

Pembrolizumab and Trastuzumab in Combination With FLOT in the Perioperative Treatment of HER2-positive, Localized Esophagogastric Adenocarcinoma - A Phase II Trial of the AIO Study Group - PHERFLOT -

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 31 (actual)
• Sponsor: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The study is an open-label, single arm, multicenter phase II trial investigating the clinical activity of a perioperative therapy consisting of a combination of pembrolizumab, trastuzumab and FLOT, followed by pembrolizumab plus trastuzumab alone for a maximum systemic treatment duration of one year in patients with Her-2 positive localized esophagogastric adenocarcinoma.

Detailed description

Her-2 positive patients suffering from localized esophagogastric adenocarcinoma (≥ T2 any N+ or any T N+) without evidence of metastatic disease will be included in the study. Eligible subjects will receive a combination of pembrolizumab and trastuzumab with FLOT 8 weeks pre- as well as post-surgery, followed by pembrolizumab and trastuzumab treatment for up to one year (maximum of 17 administrations of systemic treatment with pembrolizumab and trastuzumab incl. pre- and postoperative chemo-immunotherapy) or until tumor relapse/progression or occurrence of limiting toxicity. The primary objective of this phase II study is to demonstrate the efficacy of the FLOT/trastuzumab/pembrolizumab regimen in terms of an improvement in disease free survival (DFS) according to RECIST v1.1 and an increase in the pathological complete response (pCR) rate compared to historical controls (interim read out after surgery of last patient in study with 18 months recruitment after 24 months). Secondary objectives are further efficacy and tolerability parameters, including overall response rate according to RECIST v1.1, R0 resection rate, overall survival, safety, and tolerability (including perioperative morbidity). The exploratory objective is to assess whether clinical efficacy correlates with molecularly-defined subgroups (PD-L1 expression, MSI subtypes, and others). 30 patients will be enrolled in this trial.

Conditions

• Esophagogastric Adenocarcinoma

Interventions

Type	Name	Description
DRUG	Pembrolizumab	200 mg flat dose, IV, over 30 minutes; day 1, 22, 43 (8 weeks) pre- and post-surgery, followed by post chemotherapy phase day 1 q3w for 11 cycles; max. 17 applications
DRUG	Trastuzumab	loading dose 8 mg/kg IV over 90 min: day 1 pre- and post-surgery; maintenance dose 6 mg/kg IV over 30 min: Day 22, 43 pre- and post-surgery; followed by 6 mg/kg post chemotherapy phase, day 1 q3w for 11 cycles; max. 17 applications
DRUG	FLOT	Docetaxel 50 mg/m² IV over 1 hour plus Oxaliplatin 85 mg/m² IV over 2 hours plus Folinic Acid 200 mg/m² IV over 1 hour plus 5-FU 2600 mg/m² IV over 24 hours every 2 weeks (day 1, 15, 29, 43) for 8 weeks pre- and 8 weeks post-surgery

Timeline

• Start date: 2023-02-13
• Primary completion: 2027-10-01
• Completion: 2027-12-01
• First posted: 2022-08-17
• Last updated: 2025-06-06

Locations

13 sites across 1 country: Germany