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

Exclusion Criteria

• •Systemic antineoplastic therapy within 2 weeks prior to day -14 (Dose Escalation, Cohort A) or Cycle 1 day 1 (Dose Expansion, Cohorts B1 and B2) or 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, FUDR 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 day -14 (Dose Escalation, Cohort A) or Cycle 1 Day 1 (Dose Expansion, Cohorts B1 and B2.
• •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