A Safety and Efficacy Study of XERMELO® + First-line Chemotherapy in Patients With Advanced Biliary Tract Cancer

A Phase 2, Multicenter, Open-label, Safety and Efficacy Study of XERMELO® (Telotristat Ethyl) Plus First-line Chemotherapy in Patients With Locally Advanced, Unresectable, Recurrent or Metastatic Biliary Tract Cancer (BTC)

A Phase 2, multicenter, open-label, 2-stage study to assess the safety, tolerability, and efficacy of XERMELO in combination with first-line (1L) therapy (cisplatin [cis] plus gemcitabine [gem])

A Phase 2, multicenter, open-label, 2-stage study to assess the safety, tolerability, and efficacy of XERMELO in combination with first-line (1L) therapy cis plus gem in patients with unresectable, locally advanced, recurrent or metastatic biliary tract cancer (intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer), who are naïve to tumor-directed therapy in the locally advanced or metastatic setting, and for which treatment with 1L therapy (defined as a combination of cis plus gem) is planned.

Inclusion Criteria:

• Male or female adults, ≥18 years of age. Patients of childbearing potential must agree to use an adequate method of contraception during the study and for 30 days after the last dose of XERMELO
• Histopathologically or cytologically-confirmed, unresectable, locally advanced, recurrent, or metastatic biliary tract cancer (BTC)
• Naïve to tumor-directed therapy in locally advanced, unresectable, or metastatic setting
• Measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Plans to initiate treatment with 1L therapy (cisplatin plus gemcitabine)
• Ability to provide written informed consent prior to participation in any study-related procedure

Exclusion Criteria:

• Prior exposure to XERMELO, telotristat ethyl, telotristat etiprate, LX1032, or LX1606
• Primary tumor site in the ampulla of Vater
• Treatment with photodynamic therapy for localized disease or to relieve biliary obstruction in the presence of metastatic disease within the past 30 days
• Hematology laboratory values of: a. Absolute neutrophil count (ANC) ≤1,500 cells/mm^3; or b. Platelets ≤100,000 cells/mm^3; or c. Hemoglobin (Hgb) ≤9 g/dL; or d. White blood count (WBC) ≤3,000 cells/mm^3
• Hepatic laboratory values of aspartate aminotransferase (AST) or alanine aminotransferase (ALT): a. >5 x upper limit of normal (ULN) if patient has documented history of hepatic metastases; or b. >2.5 x ULN if no liver metastases are present
• Serum albumin <2.8 g/dL
• Total bilirubin >1.5 x ULN or >1.5 mg/dL
• Prothrombin time (PT) or international normalized ratio (INR) >1.5 x ULN
• Serum creatinine or serum urea >1.5 x ULN
• Estimated glomerular filtration rate (eGFR) <50 mL/min
• Positive pregnancy test, pregnant, or breastfeeding
• Any other clinically significant laboratory abnormality that would compromise patient safety or the outcome of the study
• Any clinically significant and/or uncontrolled cardiac-related abnormality that would compromise patient safety or the outcome of the study
• Myocardial infarction within the past 6 months
• Active bleeding diathesis
• Life expectancy ≤3 months
• Current complaints of persistent constipation or history of chronic constipation, bowel obstruction or fecaloma within the past 6 months
• Receiving chronic treatment with corticosteroids ≥5 mg of prednisone per day (or equivalent) or other immunosuppressive agent(s)
• History and/or uncontrolled hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), or human immunodeficiency virus (HIV)-1 or HIV-2
• History of substance or alcohol abuse within the past 2 years
• History of galactose intolerance, deficiency of Lapp lactase, or glucose-galactose malabsorption
• History of malignancy or active treatment for malignancy within 5 years
• Receipt of live, attenuated vaccine or close contact with someone who has received a live, attenuated vaccine within the past 1 month
• Receipt of any investigational agent or study treatment (ie, any treatment or therapy not approved by the FDA for the treatment of BTC) within the past 30 days
• Receipt of any protein or antibody-based therapeutic agents within the past 3 months
• Treatment with any tumor-directed therapy within the past 6 months with curative intent
• Existence of any surgical or medical condition that, in the judgment of the Investigator, might compromise patient safety or the outcome of the study
• Presence of any clinically significant findings (relative to the patient population) during review of medical history or upon physical exam that, in the Investigator's or Medical Monitor's opinion, would compromise patient safety or the outcome of the study
• Evidence of brain metastases
• Unable or unwilling to communicate or cooperate with the Investigator for any reason
• Employee of Sponsor or clinical site, or relative of any member of a clinical site's staff