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 who have had standard-of-care anti-cancer therapy or therapy with investigational agents (e.g., chemotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, or other investigation agents) or large field radiotherapy within 4 weeks prior to treatment initiation.
Prior therapy with anti- CD40.
Receiving of live vaccines within 30 days prior to the treatment initiation. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, Bacillus Calmette-Guerin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist(R)) are live attenuated vaccines and are not allowed.
Major surgery within 4 weeks prior to treatment initiation.
Sequential
oxaliplatin
DrugOxaliplatin (130 mg/m2) will be administered IV on Day 1 of each cycle, every 21 days (up to 6 cycles).
capecitabine
DrugCapecitabine (750 mg/m2 every 12 hours) will be administered orally with an intermittent schedule: 2 weeks on, 1 week off, of each cycle, every 21 days (up to 6 cycles).
Keytruda
Biological/VaccinePembrolizumab (200 mg) will be given IV on Day 8 of each cycle every 21 days (up to 6 cycles).
CDX-1140
Biological/VaccineCDX-1140 (0.36-1.5 mg/kg; per assigned dose level) will be given IV on Day 8 of each cycle every 21 days (up to 6 cycles).
Phase I: Safe dose of CDX-1140 in combination with CAPOX and Keytruda(R)
Estimation of safe dose will be determined based on number of dose limiting toxicities (DLTs) experienced.
Phase II: 6-month progression free survival (PFS) probability
6-month PFS probability will be calculated using the Kaplan-Meier method.
Phase II: Overall response rate (ORR)
The fraction of participants who experience a response (PR + CR) evaluated every 9 (+/- 4) weeks. Results will be reported along with 80% and 95% two-sided confidence intervals.
Safety of CDX-1140, CAPOX and Keytruda(R) in participants with advanced BTC as determined by toxicities experienced
Any adverse events/toxicities identified will be reported by type and grade.
5-year overall survival
Participants will be assessed for survival at study visits while on study therapy and annually thereafter.
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