Volagidemab for the Treatment of Hyperglycemia in Patients with Locally Advanced or Metastatic Breast Cancer Receiving Alpelisib, The GRIP-IT Pilot Study

Inclusion Criteria

• Locally advanced (not amenable to curative surgery) or metastatic invasive breast cancer
• Age > 18 years
• Post-menopausal or pre/peri-menopausal women prescribed ovarian suppression or men prescribed leuprolide acetate (Lupron) are permitted to participate
• Histologically and/or cytologically confirmed diagnosis of estrogen receptor positive (ER+) and/or progesterone receptor positive (PgR+) breast cancer by local laboratory
• HER2-negative breast cancer defined as a negative in situ hybridization test or an immunohistochemical (IHC) status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization test (fluorescence in situ hybridization [FISH], chromogenic in situ hybridization [CISH], or silver-enhanced in situ hybridization [SISH]) is required
• Presence of one or more PIK3CA mutations in tumor tissue or plasma specimens
• Participant is eligible to receive alpelisib and fulvestrant as per current Food and Drug Administration (FDA) labeling
• Participant has experienced grade 3 or 4 hyperglycemia during treatment with alpelisib (any cycle) despite standard of care measures (e.g metformin) leading to discontinuation of alpelisib
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
• Ability to understand and the willingness to sign a written informed consent document
• Leukocytes > 3,000/mm^3
• Absolute neutrophil count > 1,500/mm^3
• Platelets > 100,000/mm^3
• Bilirubin =< 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) < 2.5 X institutional upper limit of normal
• Creatinine =< 1.5 x institutional upper limit of normal OR creatinine clearance > L/min/1.73 m^2 for subjects with creatinine levels above institutional normal

Exclusion Criteria

• Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator’s best judgment
• Radiotherapy received in =< 4 weeks prior to starting study therapy. Limited field radiation for palliation received =< 2 weeks prior to starting study therapy * Patient has not recovered to grade 1 or better from related side effects of prior radiation therapy if received (with the exception of alopecia) * Radiation to >= 25% of the bone marrow
• Established diagnosis of diabetes mellitus type 1 or uncontrolled type 2 diabetes (fasting plasma glucose level, > 140 mg per deciliter [7.7 mmol per liter], or a glycosylated hemoglobin level of > 6.4%)
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of alpelisib
• Known brain metastases
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to alpelisib or other agents used in this study
• Receiving any medications or substances that are strong CYP3A4 inducers
• A history or family history of pancreatic neuroendocrine tumors, multiple endocrine neoplasia pheochromocytoma
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is treated on study. These potential risks may also apply to other agents used in this study
• Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 3 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin. Patient has received prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy)