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This study is designed to assess the antitumor activity of combination therapy of SMT-NK (allogeneic natural killer cells) and pembrolizumab versus pembrolizumab monotherapy in patients with advanced biliary tract cancer
Full description
The term of biliary tract cancer (BTC) refers to all tumors that arise from the biliary tract or the biliary drainage system, including the gallbladder.Biliary tract cancer is one of the most poorly prognosis cancers and the five-year survival rate remains at about 10% as it is difficult to expect long-term survival due to frequent local recurrence and remote metastasis after surgery.
South Korea belongs to a country with a high number of biliary tract cancer patients, and the incidence of biliary tract cancer is actually increasing every year.According to the 2018 National Cancer Registration Statistics, the number of 5-year biliary tract cancer patients was 13,967 (7,547 men and 6,420 women), which corresponds to about 2.9% of all cancersand the 5-year survival rate of biliary tract cancer patients between 2014 and 2018 was 28.8%, showing a lower survival rate than other cancer species.
Most of the long-term survival is due to early detection by screening, but advanced carcinoma is a refractory carcinoma with a 5-year survival rate of less than 5%.In addition to standard anticancer drugs, alternative anticancer drugs and targeted treatments can be developed for cancer with a large number of patients, but biliary tract cancer is difficult to find any more treatments if standard treatment fails and standard anticancer treatments cannot be continued due to resistance.
Natural killer cells (NK cells) are innate lymphocyte cells with cell killing activity, and have the characteristic of destroying cells by secretion of and granzyme into cancer cells and abnormal cells that are reduced or deficient in expression of MHC class I.Clinical studies using natural killer cells as anticancer drugs have long been conducted on various cancers.
Pembrolizumab is a monoclonal antibody designed to bind to a receptor called PD-1, which is expressed by immune cells such as T cells.Natural killer cells were also found to be expressing PD-1 in the same way as T cells, and in particular, PD-1 was found to be higher in cancer patients than in healthy people.
Therefore, combined therapy with the immune-check point such as pembrolizumab can be useful in elevating the anticancer activity of NK cells.
Enrollment
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Inclusion criteria
Patients who received a histopathological or cytologic diagnosis of nonresectable, advanced biliary tract carcinoma (intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer) and patients with refractory disease after chemotherapy and/or patients who have difficulty with chemotherapy due to side effects of chemotherapy.
Patients who receives an explanation from the trial manager about the purpose, contents, and characteristics of the Investigational products for the clinical trial and is signed by the person, guardian or legal representative in the written informed consent.
19 to 80 years old on day of signing informed consent.
Histopathological or cytologic diagnosis of advanced adenocarcinoma of the biliary tract and those with measurable lesions for RECIST evaluation
Have a performance status of ≤2 on the ECOG Performance Scale.
Patients who survival period is expected to be at least 3 months.
Demonstrate laboratory test results the following conditions:
Patients or partners who has agreed to the appropriate use of contraceptives by two or more during the treatment period (including Survival follow-up period) (for men, those who have agreed not to provide sperm)
Patients who meet one or more of the following conditions:
Patients have at least 1% Combined Positive Score (*CPS) PD-L1 expression detected on the tumor, as determined by **immunohistochemistry performed by a central laboratory.
CPS = (number of PD-L1 positive tumor cells, lymphocytes, macrophage)/ (total number of viable tumor cells) X 100
Immunohistochemistry: IHC 22C3 pharmDx test
② Patients who have a positive MSI-H or dMMR test
MSI-H was measured by PCR, and positive finding when two or more unstable markers were detected in PCR for 5 microsatellite markers, **dMMR is analyzed by immunohistochemical staining and positive when the discovery of one or more genes in MLH1, MSH2, MSH6 and PMS2 staining is lost.
Exclusion criteria
Patients who have previous history
Has a diagnosed and/or treated additional malignancy within 5 years prior to signing informed consent except for curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin
Has a previous history of anti-angiogenic agent treatment before signing informed consent
Has a known serious allergic history
Has a known serious mental illness
Identified the following in Screening:
Has received chemotherapy not less than 4 weeks old before randomization
Has received a live vaccine within 4 weeks before randomization
Is currently participating in or has participated in another clinical study within 4 weeks before randomization or the adverse event due to investigational drug administered remain before randomization
Has previously administrated Pembrolizumab and another anti-PD-1/PD-L1 agent
Has previously administrated immune-cell therapy (including natural killer cell etc.)
Female who are pregnant, breastfeeding or intending to become pregnant during the study period.
Has a history of any contraindication or has a severe hypersensitivity to any components of pembrolizumab
Has performed major surgery within 4 weeks prior to signing informed consent
Patients who are unsuitable to participate in clinical trials by investigator's decision
Primary purpose
Allocation
Interventional model
Masking
128 participants in 2 patient groups, including a placebo group
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Central trial contact
JUNGMIN IM; HAEJIN IM
Data sourced from clinicaltrials.gov
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