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

Inclusion Criteria: 1. The patient (or legally acceptable representative if applicable) provides written informed consent for the trial. 2. Be 18 years of age on day of signing informed consent. 3. Have historically confirmed histological diagnosis of metastatic ER/PR+/HER2(-) subtype breast cancer 1. HR+: Positive for estrogen receptor and/or progesterone receptor staining, indicated by ≥1% immunoreactive tumor nuclei 2. 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 4. 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. 5. 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.) 6. Have documented objective radiographic or clinical disease progression after treatment with estrogen-targeted therapies with at least one CDK4/6 inhibitor. 7. 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). 8. 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. 9. 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. 10. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 11. Have life expectancy of 3 months or greater as determined by the treating physician. 12. Have a negative PCR test at screening for SARS-COV-2 RNA. 13. Have adequate organ function (all screening labs should be performed within 10 days prior to treatment initiation): 14. Female patients of childbearing potential must have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 15. A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies 1. Not a woman of childbearing potential (WOCBP) 2. A WOCBP who agrees to follow contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment. 16. Be willing and have the ability to comply with scheduled visits (including geographical proximity), treatment plans, laboratory tests, and other study procedures. Exclusion Criteria: The patient must be excluded from participating in the trial if the patient: 1. 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). 2. 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. 3. 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. 1. 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. 2. 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. 4. 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. 5. 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. 6. Has had an allogeneic tissue/solid organ transplant. 7. 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. 8. 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. 9. 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. 10. Has known active CNS metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment. 11. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients. 12. Had previous exposure to Imprime PGG. 13. Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. 14. Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis/ interstitial lung disease. 15. Has an active infection requiring systemic therapy. 16. Has known history of active tuberculosis. 17. Has a known history of HIV infection. No HIV testing is required unless mandated by local health authority. 18. Has a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. a. Note: No testing for Hepatitis B and Hepatitis C is required unless mandated by a local health authority. 19. Has a clinically significant cardiovascular disease such as unstable angina, myocardial infarction, or acute coronary syndrome within ≤ 6 months prior to start of study treatment, symptomatic or uncontrolled arrhythmia, congestive heart failure, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification. 20. Has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, contraindicate the patient in the clinical study. 21. Has a known psychiatric or substance abuse disorder that would interfere with the patient's ability to cooperate with the requirements of the study. 22. A WOCBP who has a positive urine pregnancy test (within 72 hours) prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 23. Is breast feeding or expecting to conceive children within the projected duration of the trial, starting with the prescreening or screening visit through 120 days after the last dose of trial treatment. 24. Is a first-degree relative of the investigator, study staff or study sponsor.