Sacituzumab Govitecan +/- Pembrolizumab In HR+ / HER2 - MBC

Inclusion Criteria

• •Participants must have histologically or cytologically confirmed invasive breast cancer with unresectable locally advanced or metastatic disease. Participants without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation, i.e. visible chest wall disease or metastases on imaging meeting standard radiology criteria (i.e. lymph nodes larger than 1 cm in the short axis diameter).
• •Participants must have HR-positive, HER2-negative breast cancer (ER\>1% and/or, PR\>1%, HER2-negative per ASCO CAP guidelines) on local pathology review. If a patient has more than one histological result, the most recent sample will be considered for inclusion.
• •Participants must have either progressed on or within 12 months of adjuvant endocrine therapy or have progressed on at least one line of endocrine therapy for metastatic disease, and be considered appropriate candidates for chemotherapy.
• •Participants must have evaluable or measurable disease per RECIST 1.1. For instance, patients with bone only disease will be allowed to participate.
• •Participants must agree to undergo a research biopsy, if tumor is safely accessible, at baseline. Previously collected archival tissue will also be obtained on all participants. Tissue needs to be located and availability confirmed at time of registration. Participants must agree to a mandatory repeat biopsy 3-6 weeks after starting treatment, if tumor is safely accessible.
• •Prior chemotherapy: Participants may have received 0-1 prior chemotherapeutic regimens for metastatic breast cancer and must have been off treatment with chemotherapy for at least 14 days prior to study treatment initiation. If a prior chemotherapy was given for less than 1 cycle, it will not be counted as a prior line. No prior irinotecan or topoisomerase I-containing antibody drug conjugates in the metastatic or neo/adjuvant setting are allowed. All toxicities related to prior chemotherapy must have resolved to CTCAE v5.0 grade 1 or lower, except alopecia can be any grade and neuropathy can be grade 2 or lower.
• •Prior biologic therapy: Patients must have discontinued all biologic therapy at least 14 days prior to study treatment initiation. All toxicities related to prior biologic therapy must have resolved to CTCAE v5.0 grade 1 or lower.
• •Prior targeted therapy: Targeted therapy must have been discontinued ≥ 14 days prior to initiation of study therapy. All toxicities related to prior targeted therapy must have resolved to CTCAE v5.0 grade 1 or lower.
• •Prior radiation therapy: Patients may have received prior radiation therapy. Radiation therapy must be completed at least 7 days prior to the initiation of study treatment (at least 7 days for SRS), and all toxicities related to prior radiation therapy must have resolved to CTCAE v5.0 grade 1 or lower, unless otherwise specified per protocol. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• •Previously treated brain metastases are permitted, with the following provisions:
• •* Prior SRS should complete ≥ 7 days before study treatment initiation
• •* Prior WBRT should complete ≥ 7 days before study treatment initiation.
• •* Any corticosteroid use for brain metastases must have been discontinued for ≥ 7 days prior to study treatment initiation.
• •Participants on bisphosphonates or RANK ligand inhibitors may continue receiving therapy during study treatment and also may initiate therapy with these agents on study if clinically indicated.
• •The subject is ≥ 18 years old.
• •ECOG performance status 0-1 (Karnofsky \> 60%).
• •Participants must have normal organ and marrow function as defined below:
• •* Absolute neutrophil count ≥1,000/mcL
• •* Platelets ≥100,000/mcL
• •* Hemoglobin ≥ 9.0 g/dl
• •* INR/PT/aPTT ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is in therapeutic range of anticoagulant
• •* Total bilirubin ≤1.5 × institutional upper limit of normal (ULN) (or ≤2.0 x ULN in patients with documented Gilbert's Syndrome)
• •* AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN or ≤5 × institutional ULN for participants with documented liver metastases
• •* Serum creatinine ≤1.5 × institutional ULN OR creatinine clearance ≥ 30 mL/min/ 1.73m2 for participants with creatinine levels above institutional ULN.
• •Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 2 weeks prior to study treatment initiation. Childbearing potential is defined as participants who have not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause) and have not undergone surgical sterilization (removal of ovaries and/or uterus).
• •Women of childbearing potential (WOCBP) must agree to use an adequate method of contraception. Contraception is required starting with the first dose of study medication through 180 days (6 months) after the last dose of study medication. Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, and copper intrauterine devices. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. Hormonal contraceptives are contraindicated for HR+ breast cancer.
• •Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment with pembrolizumab and 3 months after the last dose of study treatment.
• •The participant must be capable of understanding and complying with the protocol and willing to sign a written informed consent document.
• •Participant has a known history of human immunodeficiency virus (HIV), Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as detected HCV RNA \[qualitative\]) infection. HIV-positive participants are ineligible due to the potential for pharmacokinetic interactions of combination antiretroviral therapy with study drugs and the increased risk of fatal infections. Note: No testing for HIV, Hepatitis B, or Hepatitis C is required unless mandated by local health authority.
• •The participant has received a live vaccine within 28 days prior to study treatment initiation. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, BCG, and typhoid vaccine. The use of the inactivated seasonal influenza vaccine is allowed.
• •Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.