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
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 pa...
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MDPI AG
2022-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/17/4229 |
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| author | Galam Leem Sung-Ill Jang Jae-Hee Cho Jung Hyun Jo Hee Seung Lee Moon Jae Chung Jeong Youp Park Seungmin Bang Da-Kyung Yoo Hyo-Cheon Cheon Jae-Eun Kim Kyeong-Pill Lim In-Hye Jung Jung-Min Im Yong-Yoon Chung Seung Woo Park |
| author_facet | Galam Leem Sung-Ill Jang Jae-Hee Cho Jung Hyun Jo Hee Seung Lee Moon Jae Chung Jeong Youp Park Seungmin Bang Da-Kyung Yoo Hyo-Cheon Cheon Jae-Eun Kim Kyeong-Pill Lim In-Hye Jung Jung-Min Im Yong-Yoon Chung Seung Woo Park |
| author_sort | Galam Leem |
| collection | DOAJ |
| description | 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, <i>n</i> = 6; phase 2a, <i>n</i> = 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. |
| first_indexed | 2024-03-10T01:59:23Z |
| format | Article |
| id | doaj.art-f9a3fa4e69b248989d3afc13b9f3e2a8 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T01:59:23Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f9a3fa4e69b248989d3afc13b9f3e2a82023-11-23T12:52:00ZengMDPI AGCancers2072-66942022-08-011417422910.3390/cancers14174229Safety 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 TrialGalam Leem0Sung-Ill Jang1Jae-Hee Cho2Jung Hyun Jo3Hee Seung Lee4Moon Jae Chung5Jeong Youp Park6Seungmin Bang7Da-Kyung Yoo8Hyo-Cheon Cheon9Jae-Eun Kim10Kyeong-Pill Lim11In-Hye Jung12Jung-Min Im13Yong-Yoon Chung14Seung Woo Park15Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, KoreaDepartment of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, KoreaDepartment of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, KoreaDivision of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, KoreaDivision of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, KoreaDivision of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, KoreaDivision of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, KoreaDivision of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, KoreaResearch Institute of Cell Biology, SMT Bio Co., Ltd., Seoul 08503, KoreaResearch Institute of Cell Biology, SMT Bio Co., Ltd., Seoul 08503, KoreaResearch Institute of Cell Biology, SMT Bio Co., Ltd., Seoul 08503, KoreaResearch Institute of Cell Biology, SMT Bio Co., Ltd., Seoul 08503, KoreaResearch Institute of Cell Biology, SMT Bio Co., Ltd., Seoul 08503, KoreaResearch Institute of Cell Biology, SMT Bio Co., Ltd., Seoul 08503, KoreaResearch Institute of Cell Biology, SMT Bio Co., Ltd., Seoul 08503, KoreaDivision of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, KoreaBackground 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, <i>n</i> = 6; phase 2a, <i>n</i> = 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.https://www.mdpi.com/2072-6694/14/17/4229allogeneic natural killer cell therapypembrolizumabimmunotherapychemotherapy-refractory advanced biliary tract cancer |
| spellingShingle | Galam Leem Sung-Ill Jang Jae-Hee Cho Jung Hyun Jo Hee Seung Lee Moon Jae Chung Jeong Youp Park Seungmin Bang Da-Kyung Yoo Hyo-Cheon Cheon Jae-Eun Kim Kyeong-Pill Lim In-Hye Jung Jung-Min Im Yong-Yoon Chung Seung Woo Park 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 Cancers allogeneic natural killer cell therapy pembrolizumab immunotherapy chemotherapy-refractory advanced biliary tract cancer |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | allogeneic natural killer cell therapy pembrolizumab immunotherapy chemotherapy-refractory advanced biliary tract cancer |
| url | https://www.mdpi.com/2072-6694/14/17/4229 |
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