A Phase I/II Study of CDX-1140, a CD40 Agonist, in Combination With Capecitabine and Oxaliplatin (CAPOX) and Keytruda in Subjects With Biliary Tract Carcinoma (BTC)
Background: Biliary tract carcinoma (BTC) is cancer of the slender tubes that carry fluids in the liver. People with advanced BTC have few treatment options, and their survival rates are very low.
Objective: To test a study drug (CDX-1140) combined 3 other drugs (capecitabine, oxaliplatin, Keytruda) in people with BTC.
Eligibility: Adults aged 18 years or older with BTC that progressed after treatment and is not eligible for surgery or liver transplant.
Design: Participants will be screened. They will have a physical exam. They will have blood tests and tests of their heart function. They will have imaging scans. They may need to have a biopsy: A small sample of tissue will be taken from their tumor using a small needle. Three of the drugs are given through a tube attached to a needle inserted into a vein in the arm (intravenous). The fourth drug is a pill taken by mouth with water. Participants will be treated in 21-day cycles. They will receive intravenous treatments on day 1 and day 8 of the first 6 cycles. After that, they will receive intravenous treatments only on day 1 of each cycle. Participants will take the pill twice a day only for the first 2 weeks of each cycle. They will stop taking this drug after 6 cycles. Imaging scans will be repeated every 9 weeks. Participants may continue receiving the study treatment for up to 2 years. Follow-up visits, including imaging scans, will continue for 3 more years. These images may be taken at other locations and sent to the researchers.
⁃ Participants must have histopathological confirmation of BTC or histopathological confirmation of carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of BTC.
• The maximum tumor size of any individual tumor or metastasis must be \<= 8 cm.
• Participants should have progressed on standard of care first line systemic treatment or refused standard treatment.
• Participants must have a disease that is not amenable to potentially curative resection or liver transplantation.
• Participants must have evaluable or measurable disease per RECIST 1.1
• ECOG performance status of 0 to 1
• Participants must have adequate organ and marrow function as defined below:
⁃ Absolute neutrophil count
⁃ (ANC) \>= 1,000/mcL
⁃ Platelets \>= 100,000/mcL
⁃ Total bilirubin \<= 2.5 x ULN
⁃ ALT and AST \<= 5 x ULN.
⁃ Creatinine OR Measured or calculated creatinine clearance (CrCl) (estimated glomerular filtration rate (eGFR) may also be used in place of CrCl)
⁃ \<1.5x institution upper limit of normal OR
⁃ \>= 45 mL/min/1.73 m2 for participant with creatinine levels
⁃ \>= 1.5 X institutional ULN
• Age \>=18 years.
• Participants must have recovered from any acute toxicity related to prior therapy, including surgery. Toxicity should be \<= grade 1. Note: participants with thyroid dysfunction caused by prior therapy including the need for chronic therapy are eligible.
⁃ Individuals of child-bearing potential (IOCBP) and individuals able to father a child must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) at the study entry, for the duration of study treatment and up to 4 months after the last dose of the CDX-1140 or Keytruda(R) (all individuals), 9 months (IOCBP), 6 months (individuals able to father a child) after completion of CAPOX therapy whatever comes later
⁃ Nursing participants must be willing to discontinue nursing from study treatment initiation through 4 months after study treatment discontinuation.
⁃ HBV-infected participants must be on antivirals and have HBV DNA \<100 IU/mL. HCV-infected participants can be enrolled if HCV RNA level is undetectable.
⁃ Participants must be able to understand and willing to sign a written informed consent document.