The purpose of this study is to determine the safety of peri-operative gemcitabine, cisplatin, and pembrolizumab in patients with BTC, as well as whether the combination of gemcitabine, cisplatin, and pembrolizumab (gem/cis/pembro) is feasible and lead to pathologic responses.
Must have a newly diagnosed, biopsy-proven biliary tract cancer (BTC) including gallbladder, intrahepatic, extrahepatic, and hilar cholangiocarcinoma.
Resectable BTC (biliary tract cancer)
Measurable disease per RECIST 1.1 as determined by the investigator.
Age ≥18 years.
Receiving, or previously received, any systemic chemotherapy, or investigational agent for BTC.
Has received prior radiotherapy within 2 weeks of start of study intervention.
Patients with a history of prior treatment with anti-PD-1 and anti-PD-L1.
Have been diagnosed with another cancer or myeloproliferative disorder whose natural history or treatment has the potential to interfere with safety or efficacy assessment of this study's investigational drugs.
Single group
Gemcitabine
DrugPatients will receive treatment on Day 1 and Day 8 of each cycle. Gemcitabine (1000 mg/m2) will be administered IV on Day 1 and Day 8 of each cycle, Q3 weeks with 2 - 4 cycles prior to surgery and then 4-6 cycles after surgery.
Cisplatin
DrugPatients will receive treatment on Day 1 and Day 8 of each cycle. Cisplatin (25 mg/m2) will be administered IV on Day 1 and Day 8 of each cycle, Q3 weeks with 2 - 4 cycles prior to surgery and then 4-6 cycles after surgery.
Pembrolizumab
DrugPatients will receive treatment on Day 1 of each cycle. Pembrolizumab (200 mg) will be administered IV on Day 1 of each cycle, Q3 weeks with 2 - 4 cycles prior to surgery and then 4-6 cycles after surgery. Pembrolizumab (400 mg) will be administered IV Q6 weeks up to 4 cycles as maintenance.
Average minimum Euclidean distance from CD8+ T cells to immunosuppressive tumor-associated macrophages (TAMs) at the per-cell level in patients with a major pathologic response versus pathologic non-responders.
The evaluable population of this endpoint consist of all patients who receive at least one dose of study drug and have TAMs and CD8 T cell measures at the time of surgery. TAMs being evaluated are the following: immunosuppressive TAMs with high Arginase-1 expression (CD68+CD163+Arg-1hiPDL1-/+), immunosuppressive TAMs with low Arginase-1 expression (CD68+CD163+Arg-1lo PDL1-/+), and less immunosuppressive TAMs (CD68+CD163-HLA-DRhi/CD86hi/PDL1hi)
Number of participants experiencing grade 3 or above drug-related toxicities
When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v5.0) will be counted only once for a given subject.
Number of patients proceeding to surgery without an extended treatment-related delay as a measure of feasibility
Extended treatment delay is defined as a delay of greater than 60 days of the pre-planned surgical evaluation date, or inability to go to surgery due to an adverse event related to study treatment.
Major pathologic response rate
The number of participants with a major pathologic response as defined by ≤ 10% residual viable tumor cells in the resection of the primary tumor and lymph nodes.
R0 resection rate
The number of participants with a R0 resection as defined by a microscopically margin-negative resection, in which no tumor (gross or microscopic) remains in the primary tumor bed.
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Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Lead sponsor
Merck Sharp & Dohme LLC
Collaborator
