Trifluridine/Tipiracil and Talazoparib for the Treatment of Patients With Locally Advanced or Metastatic Colorectal or Gastroesophageal Cancer

- Histologically or cytologically confirmed CRC or EGC adenocarcinoma that is locally advanced or metastatic

- Has received at least one prior line of therapy with progression or intolerance

- Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present

- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

- Life expectancy >= 3 months by investigator assessment

- Hemoglobin >= 9 g/dL

- Absolute neutrophil count >= 1500/mm^3

- Platelet count >= 100,000/mm^3 without transfusion or growth factor support

- Creatinine < 1.5 upper limit of normal (ULN) or creatinine clearance > 60 mL/min

- Total bilirubin < 1.5 x ULN

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN or < x 5 ULN in the presence of liver metastasis

- Albumin > 3 g/dL

- Ability to swallow oral medications

- Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately

- Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

- Systemic antineoplastic therapy within 2 weeks prior to initiation of FTD/TPI run-in phase (within the past 6 weeks if this treatment is mitomycin C or nitrosourea)

- Radiotherapy within the past 2 weeks excluding palliative radiotherapy to painful bone lesions

- Prior treatment with PARP inhibitor or FTD/TPI

- Any condition that in the investigator's opinion can limit absorption of FTD/TPI or talazoparib from the gastrointestinal (GI) tract

- Gastrointestinal obstruction (without diversion) or perforation within 4 weeks from initiation of FTD/TPI run-in

- Refractory ascites (requiring weekly or more frequent paracentesis or permanent indwelling peritoneal catheter)

- Untreated central nervous system (CNS) disease. Patients with leptomeningeal disease are ineligible but patients with treated, stable CNS metastasis for at least 4 weeks are allowed to participate

- Significant cardiac disease defined as congestive heart failure stage III or IV (New York Heart Association [NYHA]), acute coronary event, cerebrovascular event, peripheral arterial embolic event, venous thromboembolic event (pulmonary embolism or lower extremity deep vein thrombosis), or ventricular arrhythmia within the past 3 months

- Other malignancy requiring active therapy

- Presence of toxicities from prior therapy of grade 2 or higher

- Active infection requiring antibiotic therapy

- Known human immunodeficiency virus (HIV) or hepatitis B infection or untreated hepatitis C infection. Patients with treated hepatitis C infection and undetectable viral load are allowed to participate

- Any history of myelodysplastic syndrome, acute leukemia, or bone marrow transplant

- Pregnant or nursing female participants

- Unwilling or unable to follow protocol requirements

- Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug