Allogeneic NK Cell ("SMT-NK") in Combination With Pembrolizumab in Advanced Biliary Tract Cancer
- Conditions
- Biliary Tract Cancer
- Interventions
- Biological: 'SMT-NK' Inj (allogeneic Natural Killer cell)
- Registration Number
- NCT03937895
- Lead Sponsor
- SMT bio Co., Ltd.
- Brief Summary
The term of biliary tract cancer (BTC) or cholangiocarcinoma refers to all tumors that arise from the biliary tract or the biliary drainage system, including the gallbladder. According to the data from National Cancer Information Center in 2016, annual incidence of the cancer in Korea is 6,685 (13.1 per 100,000 population) which corresponds to about 2.9% of all cancers.
BTC is one of the most prognostic cancer with less than 30% of 5-year survival rate and the case with long-term survival can be possibly done with early detection of the cancer. However, most of BTC is found in advanced stages due to the difficulty of early detection, resulting in that the 5-year survival rate of the advanced BTC becomes less than 3%. More than 50% of the patients depends on Gemcitabine based chemotherapy but response rate of the chemotherapy remains around 30%. Thus, improving the survival rate with the standard chemotherapy is very limited and furthermore selection of second-line therapy is not easy. For this reason, development of an alternative therapeutic agent is urgently required.
NK (natural killer) cells are important cytotoxic innate immune cells that are involved in the elimination of cancer cells. Two main NK cell subsets have been defined on the basis of CD56 and CD16 expression: CD56\^brightCD16- NK subset produces abundant cytokines including interferon-γ (IFN-γ) and tumor necrosis factor-α, whereas CD56\^dimCD16+ NK subpopulation has high cytolytic activity and releases the granules containing perforin and granzymes.
Various clinical studies have been conducted to treat cancers using NK cells worldwide including Korea and therapeutic clinical results are shown for various cancers. The clinical application of NK cells is carried out by culturing and activating the NK cells isolated from blood of either patient (autologous) or blood donor (allogeneic). Recently, NK cell therapy for cholangiocarcinoma has been successfully done (NCT03358849) with allogeneic NK cell, showing safety and potential efficacy.
Like T cells, a recent study with digestive cancer has shown that NK cells also express PD-1, especially with more number of PD-1 in cancer patients than in healthy individuals, suggesting that blocking PD-1 can be used as a potential strategy to increase the anticancer activity of NK cells. Therefore, combined therapy with the immune-check point such as pembrolizumab can be useful in elevating the anticancer activity of NK cells.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Experimental: single arm Pembrolizumab Injection [Keytruda] * Biological: 'SMT-NK' Inj. (allogeneic Natural Killer cell) weekly administration for 2 weeks. After that, 1 week is a withdrawal period. (Phase 1: up to \*cycle 3, Phase 2a: up to cycle 9) * Drug: Pembrolizumab administration of Pembrolizumab 200mg/m2 at first week during cycle. * Cycle: 1 cycle is 3 weeks in total.'SMT-NK' Inj is administered at first and second week, and Pembrolizumab is administered at first week. The third week is a withdrawal period. Experimental: single arm 'SMT-NK' Inj (allogeneic Natural Killer cell) * Biological: 'SMT-NK' Inj. (allogeneic Natural Killer cell) weekly administration for 2 weeks. After that, 1 week is a withdrawal period. (Phase 1: up to \*cycle 3, Phase 2a: up to cycle 9) * Drug: Pembrolizumab administration of Pembrolizumab 200mg/m2 at first week during cycle. * Cycle: 1 cycle is 3 weeks in total.'SMT-NK' Inj is administered at first and second week, and Pembrolizumab is administered at first week. The third week is a withdrawal period.
- Primary Outcome Measures
Name Time Method Phase 1 - Dose Limiting Toxicity of the dose of 'SMT-NK' Inj. in combination with Pembrolizumab. Up to 9 weeks from Baseline. DLT (Dose Limiting Toxicity) Assessment
Phase 2a - Objective Response Rate (ORR) Up to 27 weeks from Baseline. ORR (Objective Response Rate, sum of PR and CR) is finally evaluated In the third tumor response evaluation by CT(according to RECIST V1.1).
- Secondary Outcome Measures
Name Time Method Phase 2a - Toxicity (according to CTCAE 5.0) Up to 39 weeks from Baseline Levels of adverse events and changes of experimental parameters are described according to CTCAE (version 5.0). Defined as incidence and severity of adverse events, significant laboratory changes, changes in vital signs, incidence of concomitant medications, changes from baseline over time in ECOG PS/100-mm Visual Analog Score for pain, incidence of dose adjustments over the treatment period.
Phase 2a - Time to Progression Up to 39 weeks from Baseline The length of time from the baseline until determine to progressive disease(PD).
Trial Locations
- Locations (2)
Gangnam Severance Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital
🇰🇷Seoul, Korea, Republic of