NCT04839471

BI-754091 and Afatinib for Refractory Esophageal Squamous Cell Carcinoma (BEAR Study)

BI-754091 and Afatinib for Refractory Esophageal Squamous Cell Carcinoma (BEAR Study): a Single-arm, Phase II Study

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 49 (actual)
• Sponsor: National Health Research Institutes, Taiwan · Academic / Other
• Sex: All
• Age: 20 Years
• Healthy volunteers: Not accepted

Summary

This is an open-label, single arm, multi-center study, assessing efficacy and safety of BI-754091 in combination with afatinib as treatment in patients with advanced or metastatic ESCC refractory to at least 1 line of systemic treatment (including chemotherapy or radiation therapy).

Detailed description

Esophageal cancer (EsC) is the sixth leading cancer in the world and is a complex disease with heterogenous subgroups. The squamous cell carcinoma subgroup usually involves the upper part of esophagus and typically occurs in mid-age males. Standard treatment for esophageal squamous cell carcinoma (ESCC) utilizes a trimodality approach comprising of surgery (including resection and reconstruction and/or feeding tube support), radiotherapy and chemotherapy. Addition of tyrosine kinase inhibitors has not shown a benefit in advanced or metastatic ESCC. Immunotherapy, especially checkpoint inhibitors that target the PD-1/PD-L1 axis, have demonstrated clinical benefit in phase III trials for head neck squamous cell carcinoma (HNSCC). This led to the anticipation that immunotherapy could also be useful ESCC due to similar histologic cell types, but before the results presented from KEYNOTE-181, no phase III trial have proven such benefit. It must be emphasized that KEYNOTE-180, KEYNOTE-181 and ONO-4538-07 demonstrated efficacy of immune checkpoint inhibitors in ESCC patients were only 14.3-17%; furthermore, USFDA approved pembrolizumab monotherapy for second line treatment in advanced esophageal cancer only with CPS score≧10. Thus, the benefit of immunotherapy in patients with CPS score less than 10 remains uncertain. With effective target therapy and immunotherapy options lacking, there is a huge unmet need for chemotherapy resistant, advanced or metastatic ESCC. In light of a recent retrospective cohort study demonstrating clinical benefit of using pembrolizumab combined with afatinib for refractory HNSCC, the investigators decide to implement the similar regimen (afatinib plus BI704591) in ESCC patients who had failed multiple lines of chemotherapy

Conditions

• Esophageal Squamous Cell Carcinoma (ESCC)

Interventions

Type	Name	Description
DRUG	BI-754091 plus afatinib	Eligible patients will receive BI-754091 240 mg on D1, afatinib 30 mg/day on day 1 to 21 in a 3-week cycle.

Timeline

• Start date: 2021-08-06
• Primary completion: 2023-07-24
• Completion: 2024-06-19
• First posted: 2021-04-09
• Last updated: 2024-07-08

Locations

4 sites across 1 country: Taiwan