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

NCT05159778 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: PGG-BCA2121 / MK-3475-C99
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 16

Brief 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.

Conditions

Malignant Neoplasm of Breast

Keywords

ER/PR+/ HER2(-) metastatic breast cancer

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  ORR by RECIST v1.1 following treatment with Imprime PGG + pembrolizumab

  Within 24 months of last patient enrolled

Secondary Outcomes (11)

• Median Progression Free Survival (mPFS)

  Within 24 months of last patient enrolled

• PFS at 6, 9, 12, 18, and 24 months

  Within 24 months of last patient enrolled

• Median Overall Survival (mOS)

  Within 48 months of last patient enrolled

• OS rates at 6, 9, 12, 18, 24 months

  Within 24 months of last patient enrolled

• Disease Control Rate (DCR)

  Within 24 months of last patient enrolled

Study Arms (1)

Experimental

EXPERIMENTAL

Biological: Imprime PGG; Biological: Pembrolizumab

Interventions

Imprime PGG BIOLOGICAL

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.

Also known as: Imprime, BTH-1677

Experimental

Pembrolizumab BIOLOGICAL

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.

Also known as: Keytruda

Experimental

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Be 18 years of age on day of signing informed consent.
• Have historically confirmed histological diagnosis of metastatic ER/PR+/HER2(-) subtype breast cancer
• HR+: Positive for estrogen receptor and/or progesterone receptor staining, indicated by ≥1% immunoreactive tumor nuclei
• HER2-: Immunohistochemistry assay demonstrating no or faint staining in ≤10% of tumor cells (IHC score of 0 to 1+) or negative by dual probe in situ hybridization assay
• Have peripheral blood levels of IgG anti-β-glucan antibody (ABA) of greater than, or equal to 20 mcg/mL as determined by an ELISA test within 90 days prior to start of study treatment.
• Must have progressed on at least one hormone therapy (AI or SERD) + CDK 4/6 inhibitor (and alpelisib if PIK3CA mutated) and up to two lines of prior chemotherapy (i.e., capecitabine, taxanes). (Patient may have progressed after any number of hormone therapies alone or combined with small molecule inhibitors, i.e., mTOR, PIK3CA, CDK 4/6, etc.)
• Have documented objective radiographic or clinical disease progression after treatment with estrogen-targeted therapies with at least one CDK4/6 inhibitor.
• Be willing to provide an archival tissue sample and undergo one on-treatment core or excisional biopsy of a tumor lesion not previously irradiated (Formalin-fixed, paraffin embedded \[FFPE\]tissue blocks are preferred to slides).
• Have at least one radiologically measurable lesion as per RECIST v1.1 defined as a lesion that is at least 10 mm in longest diameter imaged by CT scan or MRI and obtained by imaging within 28 days prior to registration. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• a. Note: 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.
• Have resolution of all previous treatment-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy (less than or equal to Grade 2) and alopecia. If the patient received major surgery or radiation therapy of \> 30 Gy, must have recovered from the toxicity and/or complications from the intervention.
• Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Have life expectancy of 3 months or greater as determined by the treating physician.
• Have a negative PCR test at screening for SARS-COV-2 RNA.

You may not qualify if:

• The patient must be excluded from participating in the trial if the patient:
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137).
• Has received prior radiotherapy within 2 weeks of start of study treatment. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks to Study Day 1 (or within 2 weeks for kinase inhibitors or other short half-life drugs), or within 5 half-lives for a prior investigational drug and two weeks from use of an investigational device.
• Note: Patients must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Patients with ≤Grade 2 neuropathy may be eligible. Patients with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible.
• Note: If the patient had major surgery, the patient must have recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• c. Note: Patients who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention. Note:
• Administration of killed vaccines are allowed.
• Has had an allogeneic tissue/solid organ transplant.
• Has received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including G-CSF, GM-CSF, or recombinant erythropoietin) within 4 weeks prior to Study Day 1.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
• a. Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.

Sponsors & Collaborators

• HiberCell, Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (16)

The University of Arizona Cancer Center - North Campus

Tucson, Arizona, 10032, United States

Location

The University of Arizona Cancer Center

Tucson, Arizona, 85719, United States

Location

University of Colorado at Denver

Denver, Colorado, 80045, United States

Location

University of Miami and Clinics -Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Mt. Sinai (Miami)

Miami Beach, Florida, 33140, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Louisiana State University Health Sciences Center - New Orleans

New Orleans, Louisiana, 70112, United States

Location

HealthPartners Cancer Research Center

Saint Louis Park, Minnesota, 55426, United States

Location

St. Luke's Cancer Institute

Kansas City, Missouri, 64111, United States

Location

St. Vincent - Frontier Cancer Center

Billings, Montana, 59102, United States

Location

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, 87131, United States

Location

Columba University Medical Center

New York, New York, 10032, United States

Location

Stony Brook University

Stony Brook, New York, 11794, United States

Location

Thomas Jefferson University- Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania, 19107, United States

Location

Baptist Clinical Research Institute

Memphis, Tennessee, 38120, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

BTH1677; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Alison Stopeck, MD

  Stony Brook University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open label Simon 2 stage design.

Study Record Dates

• First Submitted: November 10, 2021
• First Posted: December 16, 2021
• Study Start: November 9, 2021
• Primary Completion: March 22, 2023
• Study Completion: April 12, 2023
• Last Updated: June 22, 2023

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (16)