PMID- 36077766
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220913
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 14
IP  - 17
DP  - 2022 Aug 30
TI  - Safety and Efficacy of Allogeneic Natural Killer Cells in Combination with 
      Pembrolizumab in Patients with Chemotherapy-Refractory Biliary Tract Cancer: A 
      Multicenter Open-Label Phase 1/2a Trial.
LID - 10.3390/cancers14174229 [doi]
LID - 4229
AB  - BACKGROUND AND AIM: This study investigated the administration of combination 
      therapy, allogeneic natural killer (NK) cells and pembrolizumab in the treatment 
      of advanced biliary tract cancer to determine the safety and tolerability (phase 
      1) and the efficacy and safety (phase 2a). METHODS: Forty patients (phase 1, n = 
      6; phase 2a, n = 34) were enrolled between December 2019 and June 2021. The 
      patients received highly activated allogeneic NK cells ("SMT-NK") on weeks 1 and 
      2 and pembrolizumab on week 1. This 3-week schedule (one cycle) was repeated 
      until confirmed disease progression, intolerable adverse events (AEs), patient 
      withdrawal, or finishing the maximum treatment schedule. The tumor response was 
      evaluated after every three cycles. RESULTS: In phase 1, four patients (66.7%) 
      experienced seven AEs, but no severe AE was observed. In phase 2a, 126 AEs 
      occurred in 29 patients (85.3%). Severe AEs (>/=grade 3) were reported in 16 
      patients (47.1%). The overall response rate (ORR) was 17.4% in the full analysis 
      set and 50.0% in the per-protocol set. CONCLUSIONS: SMT-NKs plus pembrolizumab 
      resulted in no severe AEs directly related to the drug combination. The 
      combination therapy also exerted antitumor activity with improved efficacy 
      compared to the recent monotherapy with pembrolizumab in patients with advanced 
      biliary tract cancer.
FAU - Leem, Galam
AU  - Leem G
AD  - Division of Gastroenterology, Department of Internal Medicine, Severance 
      Hospital, Yonsei University College of Medicine, Seoul 03722, Korea.
FAU - Jang, Sung-Ill
AU  - Jang SI
AUID- ORCID: 0000-0003-4937-6167
AD  - Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University 
      College of Medicine, Seoul 06273, Korea.
FAU - Cho, Jae-Hee
AU  - Cho JH
AUID- ORCID: 0000-0003-4174-0091
AD  - Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University 
      College of Medicine, Seoul 06273, Korea.
FAU - Jo, Jung Hyun
AU  - Jo JH
AUID- ORCID: 0000-0002-2641-8873
AD  - Division of Gastroenterology, Department of Internal Medicine, Severance 
      Hospital, Yonsei University College of Medicine, Seoul 03722, Korea.
FAU - Lee, Hee Seung
AU  - Lee HS
AUID- ORCID: 0000-0002-2825-3160
AD  - Division of Gastroenterology, Department of Internal Medicine, Severance 
      Hospital, Yonsei University College of Medicine, Seoul 03722, Korea.
FAU - Chung, Moon Jae
AU  - Chung MJ
AUID- ORCID: 0000-0002-5920-8549
AD  - Division of Gastroenterology, Department of Internal Medicine, Severance 
      Hospital, Yonsei University College of Medicine, Seoul 03722, Korea.
FAU - Park, Jeong Youp
AU  - Park JY
AD  - Division of Gastroenterology, Department of Internal Medicine, Severance 
      Hospital, Yonsei University College of Medicine, Seoul 03722, Korea.
FAU - Bang, Seungmin
AU  - Bang S
AD  - Division of Gastroenterology, Department of Internal Medicine, Severance 
      Hospital, Yonsei University College of Medicine, Seoul 03722, Korea.
FAU - Yoo, Da-Kyung
AU  - Yoo DK
AD  - Research Institute of Cell Biology, SMT Bio Co., Ltd., Seoul 08503, Korea.
FAU - Cheon, Hyo-Cheon
AU  - Cheon HC
AD  - Research Institute of Cell Biology, SMT Bio Co., Ltd., Seoul 08503, Korea.
FAU - Kim, Jae-Eun
AU  - Kim JE
AD  - Research Institute of Cell Biology, SMT Bio Co., Ltd., Seoul 08503, Korea.
FAU - Lim, Kyeong-Pill
AU  - Lim KP
AD  - Research Institute of Cell Biology, SMT Bio Co., Ltd., Seoul 08503, Korea.
FAU - Jung, In-Hye
AU  - Jung IH
AD  - Research Institute of Cell Biology, SMT Bio Co., Ltd., Seoul 08503, Korea.
FAU - Im, Jung-Min
AU  - Im JM
AD  - Research Institute of Cell Biology, SMT Bio Co., Ltd., Seoul 08503, Korea.
FAU - Chung, Yong-Yoon
AU  - Chung YY
AD  - Research Institute of Cell Biology, SMT Bio Co., Ltd., Seoul 08503, Korea.
FAU - Park, Seung Woo
AU  - Park SW
AD  - Division of Gastroenterology, Department of Internal Medicine, Severance 
      Hospital, Yonsei University College of Medicine, Seoul 03722, Korea.
LA  - eng
GR  - HI18C2044/Ministry of Health and Welfare/
PT  - Journal Article
DEP - 20220830
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC9454779
OTO - NOTNLM
OT  - allogeneic natural killer cell therapy
OT  - chemotherapy-refractory advanced biliary tract cancer
OT  - immunotherapy
OT  - pembrolizumab
COIS- The authors declare no conflict of interest.
EDAT- 2022/09/10 06:00
MHDA- 2022/09/10 06:01
PMCR- 2022/08/30
CRDT- 2022/09/09 01:11
PHST- 2022/08/07 00:00 [received]
PHST- 2022/08/28 00:00 [revised]
PHST- 2022/08/29 00:00 [accepted]
PHST- 2022/09/09 01:11 [entrez]
PHST- 2022/09/10 06:00 [pubmed]
PHST- 2022/09/10 06:01 [medline]
PHST- 2022/08/30 00:00 [pmc-release]
AID - cancers14174229 [pii]
AID - cancers-14-04229 [pii]
AID - 10.3390/cancers14174229 [doi]
PST - epublish
SO  - Cancers (Basel). 2022 Aug 30;14(17):4229. doi: 10.3390/cancers14174229.