NCT05967884

PD-1 +/- IL-4 Inhibition in ER+ Breast Cancer

A Randomized Phase II Window of Opportunity Clinical Trial of IL-4 +/- PD-1 Inhibition in Early-stage ER+ HER2- Breast Cancer

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Ottawa Hospital Research Institute · Academic / Other
• Sex: Female
• Age: 18 Years – 90 Years
• Healthy volunteers: Not accepted

Summary

This proposal is for a Window of Opportunity (WOO) clinical trial using a novel combination of two Health Canada approved agents, cemiplimab (Libtayo) and dupilumab (Dupixent), for off label use in early-stage estrogen receptor positive (ER+) breast cancer.

Detailed description

This is a phase II, open-label, randomized window of opportunity trial evaluating the immunologic effects within the tumour, microenvironment, and host blood of patients treated with either * Arm A: Cemiplimab (n=10) * Arm B: Cemiplimab + Dupilumab (n=10) administered prior to surgery. Randomization will be at 1:1 ratio in patients newly diagnosed with primary operable ER+\* HER2- invasive breast cancer awaiting surgery in the next 4-6 weeks who are not planned for neoadjuvant therapy. Primary Hypothesis: In ER+ breast cancer, blockade of IL-4 signalling using dupilumab enhances anti-tumor immunity (through reduced Th2 skewing) when used in combination with PD-1 inhibitors (Cemiplimab) compared to PD-1 inhibition alone in ER+ breast cancer Primary Objective: • To determine whether addition of dupilumab to cemiplimab reduces TH2 skewing of the tumor, tumor microenvironment (TME) and blood in patients with ER+ breast cancer Secondary Objectives: * To evaluate dynamic changes in immune cell populations as measured by in situ proteomics * To characterize the safety of a short-term duration of the combination of dupilumab with cemiplimab in patients with ER+ breast cancer awaiting surgery Exploratory Objective: • To test the effect of tumor PD-1 gene expression and its effect on the immune response in treated and untreated patients This is a window of opportunity trial which will require administration of cemiplimab or combination of cemiplimab + dupilumab prior to surgery. Surgery will be a minimum of 96 hours to 2 weeks after the cemiplimab. Patient follow-up after surgery will be for a period of 30 days post-surgery. Target: 20 patients (10 in Arm A and 10 in Arm B). Accounting for screen failures and withdrawals (20%), 24 patients will be accrued.

Conditions

• Breast Cancer

Interventions

Type	Name	Description
DRUG	Arm A: Cemiplimab, Arm B: Cemiplimab + Dupilumab	Arm A: Cemiplimab: 350mg IV x 1 dose administered prior to surgery Arm B: Cemiplimab + Dupilumab: Cemiplimab 350mg IV x 1 dose + Dupilumab 600 mg SC x 1 dose administered prior to surgery

Timeline

• Start date: 2023-08-04
• Primary completion: 2024-08-01
• Completion: 2024-08-01
• First posted: 2023-08-01
• Last updated: 2023-08-01

Locations

2 sites across 1 country: Canada