Allogeneic NK Cell ("SMT-NK") in Combination With Pembrolizumab in Advanced Biliary Tract Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03937895|
Recruitment Status : Recruiting
First Posted : May 6, 2019
Last Update Posted : January 18, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Biliary Tract Cancer||Biological: 'SMT-NK' Inj (allogeneic Natural Killer cell) Drug: Pembrolizumab Injection [Keytruda]||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 1/2a Clinical Trial for the Evaluation of Safety and Efficacy of Allogeneic NK Cell ("SMT-NK") in Combination With Pembrolizumab for Patients With Gemcitabine-refractory Biliary Tract Cancer|
|Actual Study Start Date :||December 3, 2019|
|Estimated Primary Completion Date :||February 2, 2021|
|Estimated Study Completion Date :||June 2, 2021|
Experimental: Experimental: single arm
Biological: 'SMT-NK' Inj (allogeneic Natural Killer cell)
In 120 mL, 3x10^6 (± 20%) cells/kg. weekly administration via Intravenous for 2 weeks. After that, 1 week is a withdrawal period.
Drug: Pembrolizumab Injection [Keytruda]
Administration via Intravenous of 200 mg every 3 weeks(one administration per cycle.).
- Phase 1 - Dose Limiting Toxicity of the dose of 'SMT-NK' Inj. in combination with Pembrolizumab. [ Time Frame: Up to 9 weeks from Baseline. ]DLT (Dose Limiting Toxicity) Assessment
- Phase 2a - Objective Response Rate (ORR) [ Time Frame: 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).
- Phase 2a - Time to Progression [ Time Frame: Up to 39 weeks from Baseline ]The length of time from the baseline until determine to progressive disease(PD).
- Phase 2a - Toxicity (according to CTCAE 5.0) [ Time Frame: 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03937895
|Contact: Jino Jung, B.S.||firstname.lastname@example.org|
|Contact: Jungmin Im, M.S.||email@example.com|
|Korea, Republic of|
|Gachon University Gil Medical Center||Recruiting|
|Incheon, Korea, Republic of, 21565|
|Contact: Jae Hee Cho, MD. PhD 82-32-460-2187 firstname.lastname@example.org|
|Seoul, Korea, Republic of, 03722|
|Contact: Seung Woo Park, MD. PhD 82-2-2228-1964 SWOOPARK@yuhs.ac|
|Gangnam Severance Hospital||Recruiting|
|Seoul, Korea, Republic of, 06273|
|Contact: Sung Ill Jang, MD. PhD 82-2-2019-3580 AEROJSI@yuhs.ac|
|Principal Investigator:||Seung Woo Park, MD. PhD||Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital|