NCT05159778

Phase 2 Study of Imprime PGG and Pembrolizumab in Patients With HR+/HER2- Metastatic Breast Cancer (mBCA)

A Multicenter, Open-label, Phase 2 Study of Imprime PGG and Pembrolizumab in Patients With Metastatic Breast Cancer (mBCA) Who Have Progressed Through Prior Hormonal Therapy

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 26 (actual)
• Sponsor: HiberCell, Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The primary objective of this Phase 2 Simon 2-Stage study is to determinate the Overall Response Rate (ORR) per RECIST v1.1 following treatment with Imprime PGG + pembrolizumab in patients with ER/PR+/ HER2(-) metastatic breast cancer who have progressed through prior hormone therapy with at least one CDK4/6 inhibitor, and a maximum of 2 subsequent chemotherapy treatment. Patients will be screened for baseline anti-β glucan antibody level (ABA; measured in peripheral blood). Those patients with an ABA greater than or equal to 20 mcg/ml and meeting all other I/E criteria, will be enrolled. The study will enroll 47 patients with 23 patients enrolled into Stage 1. If 4 or more patients in Stage 1 have an objective response after 12 weeks of treatment, the study will proceed into Stage 2. A total of 24 patients will be enrolled in Stage 2 for a total combined population of 47. Overall, objective responses must be observed in 10 patients for the study to be declared a success.

Detailed description

Study PGG-BCA-2121 is a multicenter, open-label, Phase 2 study of patients with metastatic breast cancer who have progressed through prior hormonal therapy with at least one CDK4/6 inhibitor, and a maximum of 2 subsequent chemotherapy treatment. All patients will be immune checkpoint inhibitor-naive. A total of 47 mBCA patients will be enrolled to treatment with the combination of Imprime PGG 4 mg/kg with pembrolizumab 200mg. Patients will be screened and enrolled if baseline ABA level is greater than or equal to 20 mcg/mL (ABA+) and if all other inclusion/ exclusion criteria are met (ABA is measured in peripheral blood). Approximately 200 patients will be screened (allows for pre/ early screening for ABA levels). Dosing will occur in three-week cycles. On Day 1 of each cycle, all patients will receive Imprime PGG 4 mg/kg IV over \~ 2-4 hr (based on body weight) followed by pembrolizumab 200 mg, IV over 30 min. On Day 8 and 15 of each cycle, patients will receive only Imprime PGG. Premedications (defined by the protocol) will be administered \~30 min before initiation of Imprime PGG during Cycles 1-3 (thereafter at the physician's discretion). Patients will dose to confirmed progression, safety event, or other administrative reason requiring discontinuation; all patients are allowed to dose up to 35 cycles. For all patients, a baseline CT/MRI will be conducted. The first scan to assess response will be conducted 12 wks post-initiation of study treatment (pre-Cycle 5) and then q12wks thereafter until confirmed progression or discontinuation. At any time, if a patient's response is progressive disease (PD), the patient will dose for an additional 4-8 wks (physician discretion) followed by a confirmatory scan. If that scan shows progressive disease, the patient will move into overall survival monitoring. Response will be assessed by RECISTv1.1 and iRECIST will be applied by the Investigator solely for clinical management of patients as described below. All scans will be read locally and by blinded central review. At screening, an official historical diagnostic pathology report +/- archival tissue (formalin-fixed paraffin embedded \[FFPE\]) will be retrieved to confirm historical diagnosis of ER/PR status. All patients will have a newly obtained core or excisional biopsy at 6 wks after initiation of study treatment. Fresh biopsies at baseline and progression or End of Treatment are strongly encouraged but not mandated. Preferably, biopsies should be non-bone and if amenable, a biopsy of a liver lesion not designated as target or non-target is preferred. Patients with bone only metastases (BOM) are not eligible, except if such lesions have a distinct, associated soft tissue component that is measurable as per RECIST 1.1. Blood samples for safety monitoring and translational endpoints will be collected on all patients as detailed in the Schedule of Activities.

Conditions

• Malignant Neoplasm of Breast

Interventions

Type	Name	Description
BIOLOGICAL	Imprime PGG	Imprime PGG is a soluble, β-1,3/1,6 glucan isolated from the cell wall of a proprietary Saccharomyces cerevisiae yeast strain. Imprime PGG acts as a Pathogen-Associated Molecular Pattern (PAMP). Imprime will be administered at a dose of 4 mg/kg IV over a 2-hour infusion time on Days 1, 8 and 15 of each 3-week treatment cycle.
BIOLOGICAL	Pembrolizumab	Pembrolizumab is a humanized monoclonal antibody against the programmed death receptor-1 protein. Pembrolizumab will be given at a fixed dose of 200 mg IV over 30 minutes on Day 1 of each 3-week treatment cycle after the Imprime infusion.

Timeline

• Start date: 2021-11-09
• Primary completion: 2023-03-22
• Completion: 2023-04-12
• First posted: 2021-12-16
• Last updated: 2023-06-22

Locations

16 sites across 1 country: United States

Regulatory

• FDA-regulated drug study