Gedatolisib and Antibody-drug Conjugate PF-06647020 in Treating Patients with Metastatic Triple Negative Breast Cancer

Inclusion Criteria

• Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information * NOTE: HIPAA authorization may be included in the informed consent or obtained separately
• Must have histologically or cytologically confirmed triple negative (estrogen receptor [ER]-/progesterone receptor [PR]-/HER2-) or estrogen poor invasive breast cancer * NOTE: ER and PR negative or estrogen poor is defined as any one of the following: ** Local pathology report classifies them as negative ** Allred score of 2 or below for ER and PR ** < 5% weakly positive staining for ER and PR * NOTE: HER2- is defined as follows: ** HER2 will be considered negative if scored 0 or 1+ by immunohistochemistry (IHC) or 2+ by IHC associated with a fluorescence in situ hybridization (FISH) ratio of < 2.0 or < 6 copies per cell
• Patients must have disease amenable to biopsy; patients who decline to undergo a biopsy for this trial will be ineligible
• Patients must have metastatic disease that is either refractory to standard therapy or for which no effective standard therapy that confers clinical benefit is available
• Patients must have received at least one prior chemotherapy regimen for metastatic disease * NOTE: Patients who received anthracycline and taxane containing adjuvant or neoadjuvant therapy and progressed within 12 months may enter this trial as their first therapy for metastatic breast cancer (MBC)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 within 14 days prior to registration for protocol therapy
• Women of childbearing potential and males must be willing to use an effective method of contraception from the time consent is signed until 4 weeks after treatment discontinuation
• Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to registration for protocol therapy * NOTE: Women are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal
• Women must not be breastfeeding
• Hemoglobin (Hgb) >= 9.0 g/dL obtained within 14 days prior to registration for protocol therapy
• Platelets >= 100 K/mm^3 obtained within 14 days prior to registration for protocol therapy
• Absolute neutrophil count (ANC) >= 1.5 K/mm^3 obtained within 14 days prior to registration for protocol therapy
• Calculated creatinine clearance of >= 50 cc/min using the Cockcroft-Gault formula obtained within 14 days prior to registration for protocol therapy
• Bilirubin =< upper limit of normal (except in patients with documented Gilbert’s disease, who must have a total bilirubin =< 3.0 mg/dL) obtained within 14 days prior to registration for protocol therapy
• Aspartate aminotransferase (AST, serum glutamic-oxaloacetic transaminase [SGOT]) =< 2.5 x upper limit of normal (ULN) (=< 5.0 x ULN in patients with known liver metastases) obtained within 14 days prior to registration for protocol therapy
• Alanine aminotransferase (ALT, serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN (=< 5.0 x ULN in patients with known liver metastases) obtained within 14 days prior to registration for protocol therapy
• Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L) (Gedatolisib can cause hyperglycemia) obtained within 14 days prior to registration for protocol therapy
• Glycosylated hemoglobin (HbA1c) =< 7 % (Gedatolisib can cause hyperglycemia) obtained within 14 days prior to registration for protocol therapy

Exclusion Criteria

• Patients who have received prior treatment with a PI3K inhibitor or have known hypersensitivity to Gedatolisib or its excipients
• Patients who have received prior treatment with an mTOR inhibitor
• Patients who have received prior treatment with PTK7-ADC (PF-06647020)
• Patients with untreated brain metastases are excluded. However, patients with metastatic central nervous system (CNS) tumors may participate in this trial, if the patient is > 4 weeks from therapy completion (including [incl.] radiation and/or surgery), is clinically stable at the time of study entry and is receiving a stable or decreasing dose of corticosteroid therapy; brain magnetic resonance imaging (MRI) or head computed tomography (CT) is required at screening for patients with known brain metastases
• Prior chemotherapy within 3 weeks of study registration
• Prior radiation within 2 weeks of study registration