Sacituzumab Govitecan in Combination With Capecitabine for Advanced Gastrointestinal Cancers After Progression on Standard Therapy

Inclusion Criteria:

• Female or male patients, 18 years of age or older, able to understand and givewritten informed consent

• Patients with the histologically or cytologically documented metastaticadenocarcinoma of gastrointestinal origin, including gastroesophageal, colorectal,and pancreaticobiliary that have failed standard therapy

• Adequate hematologic counts without transfusional or growth factor support within 2weeks of study drug initiation (hemoglobin ≥ 9 g/dL, absolute neutrophil count (ANC) ≥ 1500/mm3, and platelets ≥ 100,000/μL).

• Adequate hepatic function (bilirubin ≤ 1.5x upper limit normal (ULN), aspartateaminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5xULN or ≤ 5xULN ifknown liver metastases, and serum albumin > 3 g/dL).

• Adequate renal function (Creatinine clearance ≥ 30 mL/min as assessed by theCockcroft-Gault equation.

• Male and female patients of childbearing potential who engage in heterosexualintercourse must agree to use protocol-specified method(s) of contraception. Femalesof childbearing potential must not have had unprotected sexual intercourse within 30days before study entry and must agree to use a highly effective method ofcontraception (total abstinence [if it is her preferred and usual lifestyle], acontraceptive implant, an oral contraceptive, or have a vasectomized partner withconfirmed azoospermia) throughout the entire study period and for 6 months afterstudy drug discontinuation. For sites outside of the European Union (EU), it ispermissible that if a highly effective method of contraception is not appropriate oracceptable to the subject, then the subject must agree to use a medically acceptablemethod of contraception, ie, double barrier methods of contraception such as condomplus diaphragm or cervical/vault cap with spermicide. If currently abstinent, thesubject must agree to use a highly effective method as described above if shebecomes sexually active during the study period or for 6 months after study drugdiscontinuation. Females who are using hormonal contraceptives must have been on astable dose of the same hormonal contraceptive product for at least 28 days beforedosing and must continue to use the same contraceptive during the study and for 6months after study drug discontinuation.

• Male subjects who are partners of women of childbearing potential must use a condomand spermicide and their female partners, if of childbearing potential, must use ahighly effective method of contraception (see methods described above in InclusionCriterion 15) beginning at least 1 menstrual cycle prior to starting study drug,throughout the entire study period, and for 3 months after the last dose of studydrug, unless the male subjects are totally sexually abstinent or have undergone asuccessful vasectomy with confirmed azoospermia or unless the female partners havebeen sterilized surgically or are otherwise proven sterile.

• Willing and able to comply with the requirements and restrictions in this protocol

Exclusion Criteria:

• Positive serum pregnancy test or women who are breastfeeding.

• Known hypersensitivity to the study drug(s), its metabolites, or formulationexcipient.

• Requirement for ongoing therapy with or prior use of any prohibited medicationslisted in protocol.

• Have had a prior anticancer biologic agent within 4 weeks prior to enrolment or havehad prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to enrollment and have not recovered (i.e., ≥ Grade 2 is considerednot recovered) from adverse events (AEs) at the time of study entry. Note: patientswith any grade neuropathy or alopecia are an exception to this criterion and willqualify for the study. Note: if patients received major surgery, they must haverecovered adequately from the toxicity and/or complications from the interventionprior to starting therapy.

• Have previously received topoisomerase 1 inhibitors.

• Have an active second malignancy. Note: patients with a history of malignancy thathave been completely treated, with no evidence of active cancer for 3 years prior toenrolment, or patients with surgically cured tumors with low risk of recurrence (e.g., nonmelanoma skin cancer, histologically confirmed complete excision ofcarcinoma in situ, or similar) are allowed to enroll.

• Have unstable brain metastases. Note: Patients with stable brain metastasis can beincluded. "Stable" brain metastases may be defined as: Prior local treatment byradiation, surgery, or stereotactic surgery, imaging - stable or decreasing sizeafter such local treatment, clinically stable signs and symptoms for at least 4weeks, ≥2 weeks from discontinuation of anti-seizure medication. Patient may receivelow and stable doses of corticosteroids ≤ 20 mg prednisone or equivalent daily. Itshould be confirmed by MRI/CT scan that patient has had stable brain metastasis for 4 weeks prior to treatment.

• Met any of the following criteria for cardiac disease:

• Myocardial infarction or unstable angina pectoris within 6 months of enrolment.

• 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%.

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

• Have active serious infection requiring antibiotics.

• Have known history of HIV-1 or 2 (or positive HIV-1/2 antibody, if done atscreening) with detectable viral load OR taking medications that may interfere withSN-38 metabolism.

• 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 RNA by quantitative PCR for confirmation of activedisease. Patients with a known history of HCV or a positive HCV antibody testwill not require a HCV antibody at screening and will only require HCV RNA byquantitative PCR for confirmation of active disease.

• Patients who test positive for HIV antibody.

• Have other concurrent medical or psychiatric conditions that, in the investigator'sopinion, may be likely to confound study interpretation or prevent completion ofstudy procedures and follow- up examinations.

• Any medical condition that, in the investigator's or sponsor's opinion, poses anundue risk to the patient's participation in the study [list examples as necessary].

• Use of other investigational drugs (drugs not marketed for any indication) within 28days or 5 half-lives (whichever is longer) of first dose of study drug.