Sacituzumab Govitecan for the Treatment for Patients With Locally Advanced, Recurrent, or Metastatic Cholangiocarcinoma

Inclusion Criteria:

• Ability of participant or legally authorized representative (LAR) to understand thisstudy, and participant or LAR willingness to sign a written informed consent

• Males and females age ≥ 18 years

• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2

• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

• Women of childbearing potential must have a negative serum or urine pregnancy testwithin 7 days before day 1 of study treatment

• Locally advanced, recurrent or metastatic cholangiocarcinoma) after progressing orintolerant to at least one line of systemic therapy

• Adequate archival tissue from prior biopsy for biomarker evaluation or willingnessto undergo tissue biopsy before treatment starts and on treatment. Patients who, inthe opinion of the investigator, do not have tissue that can be safely biopsied areexempted

• Absolute neutrophil count ≥ 1.5 K/UL

• Hemoglobin ≥ 9 g/dL

• Platelets ≥ 100K/UL

• Creatinine clearance ≥ 30 mL/min as assessed by the Cockcroft-Gault equation {Cockcroft 1976} or Creatinine clearance ≥ 60 mL/min

• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) OR direct bilirubin ≤ 1 x ULN

• Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN unless livermetastases are present, in which case they must be ≤ 5 x ULN

• Women of child-bearing potential and men with partners of child-bearing potentialmust agree to practice sexual abstinence or to use the forms of contraception forthe duration of study participation and as follows:

• Females: for 6 months following completion of therapy

• Males: for 3 months following completion of therapy

Exclusion Criteria:

• Simultaneously enrolled in any therapeutic clinical trial

• Current or anticipating use of other anti-neoplastic or investigational agents whileparticipating in this study

• Treatment with chemotherapy, biologics, or investigational agents that is notcompleted 4 weeks or 5 half-lives (whichever is longer) prior to first dose of studydrug

• Diagnosed with a psychiatric illness or is in a social situation that would limitcompliance with study requirements

• Other underlying medical condition that, in the opinion of the investigator, wouldimpair the ability of the participant to receive or tolerate the planned treatmentand follow-up; any known psychiatric or substance abuse disorders that wouldinterfere with cooperating with the requirements of the study

• Is pregnant or breastfeeding

• Known homozygosity in the UGT1A1*28 allele associated with irinotecan toxicity

• Known hypersensitivity (≥ grade 3) to the study drug, its metabolites, orformulation excipient

• Requirement for ongoing therapy with (or prior use within 2 weeks of cycle 1, day 1)high dose systemic corticosteroids (≥ 20 mg of prednisone or its equivalent)

• Requirement for ongoing therapy with or prior use of UGT1A1 inhibitors/inducers

• Active grade 3 (per the National Cancer Institute [NCI] Common Terminology Criteriafor Adverse Events [CTCAE], version 5.0) or higher viral, bacterial, or fungalinfection within 2 weeks prior to the first dose of study treatment

• Have not recovered (i.e., ≥ grade 2 is considered not recovered) from adverse events (AEs) due to a previously administered agent.

• Note: patients with any grade neuropathy or alopecia are an exception to thiscriterion and will qualify for the study.

• Note: if patients received major surgery, they must have recovered adequatelyfrom the toxicity and/or complications from the intervention prior to startingtherapy

• Active central nervous system (CNS) metastases. Patients with treated CNS metastasesare permitted on study if all the following are true:

• CNS metastases have been clinically stable for at least 6 weeks prior toscreening and baseline scans show no evidence of new or enlarged metastasis.

• If requiring steroid treatment for CNS metastases, the patient is on a stabledose <10 mg/day of prednisone or equivalent for at least 2 weeks.

• Patient does not have leptomeningeal disease

• Met any of the following criteria for cardiac disease:

• Myocardial infarction or unstable angina pectoris within 6 months ofenrollment.

• History of serious ventricular arrhythmia (ie, ventricular tachycardia orventricular fibrillation), high-grade atrioventricular block, or other cardiacarrhythmias requiring antiarrhythmic medications (except for atrialfibrillation that is well controlled with antiarrhythmic medication); historyof QT interval prolongation.

• New York Heart Association (NYHA) class III or greater congestive heart failureor left ventricular ejection fraction of < 40%

• Prior treatment with topoisomerase 1 inhibitors

• Have an active concurrent malignancy or malignancy within 3 years of studyenrollment. Note: patients with a history of malignancy that have been completelytreated, with no evidence of active cancer for 3 years prior to enrollment, orpatients with surgically cured tumors with low risk of recurrence (e.g., nonmelanomaskin cancer, histologically confirmed complete excision of carcinoma in situ, orsimilar such as adequately treated basal or squamous cell carcinoma,non-melanomatous skin cancer, or curatively resected cervical cancer) are allowed toenroll

• Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease)or gastrointestinal (GI) perforation within 6 months of enrollment

• Currently receiving systemic antimicrobial treatment for active infection (viral,bacterial, or fungal) at the time of first dose of sacituzumab govitecan. Routineantimicrobial prophylaxis is permitted

• Have known history of human immunodeficiency virus (HIV)-1 or 2 (or positive HIV-1/2antibody, if done at screening) with detectable viral load

• Have active hepatitis B virus (HBV) or hepatitis C virus (HCV). In patients with ahistory of HBV or HCV, patients with detectable viral loads will be excluded.

• Patients who test positive for hepatitis B surface antigen (HBsAg). Patientswho test positive for hepatitis B core antibody (anti-HBc) will require HBV DNAby quantitative polymerase chain reaction (PCR) for confirmation of activedisease.

• Patients who test positive for HCV antibody. Patients who test positive for HCVantibody will require HCV ribonucleic acid (RNA) by quantitative PCR forconfirmation of active disease. Patients with a known history of HCV or apositive HCV antibody test will not require a HCV antibody at screening andwill only require HCV RNA by quantitative PCR for confirmation of activedisease

• Patients with active tuberculosis based on medical history

• Documented history of a cerebral vascular event (stroke or transient ischemicattack), unstable angina, myocardial infarction, or cardiac symptoms (includingcongestive heart failure) consistent with NYHA Class III-IV within 6 months prior tothe first dose of sacituzumab govitecan

• Radiotherapy or major surgery within 2 weeks prior to first dose of study drug.Patient must have recovered adequately from the toxicity and/or complications fromthe intervention prior to starting study treatment

• Administration of a live, attenuated vaccine within 30 days prior to first dose ofstudy drug. Examples of live vaccines include, but are not limited to, thefollowing: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever,rabies, BCG, and typhoid vaccine.

• Seasonal influenza vaccines for injection are generally killed virus vaccinesand are allowed; however, intranasal influenza vaccines (e.g., FluMist [registered trademark]) are live attenuated vaccines and are not allowed