An Investigator-Initiated Phase 2 Study of Nivolumab Plus Low-Dose Ipilimumab as First-Line Therapy for Microsatellite Instability—High Advanced Gastric or Esophagogastric Junction Cancer (NO LIMIT, WJOG13320G/CA209-7W7)
Nivolumab (NIVO) plus low-dose ipilimumab (IPI) has shown a promising survival benefit in first-line treatment of microsatellite instability-high (MSI-H) colorectal cancer. We hypothesized that this regimen might also be beneficial for MSI-H gastric cancer (GC), which accounts for ~5% of all GC case...
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MDPI AG
2021-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/4/805 |
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| author | Hisato Kawakami Shuichi Hironaka Taito Esaki Kazuaki Chayama Masahiro Tsuda Naotoshi Sugimoto Shigenori Kadowaki Akitaka Makiyama Nozomu Machida Hidekazu Hirano Kenro Hirata Hiroki Hara Hiroshi Yabusaki Yoshito Komatsu Kei Muro |
| author_facet | Hisato Kawakami Shuichi Hironaka Taito Esaki Kazuaki Chayama Masahiro Tsuda Naotoshi Sugimoto Shigenori Kadowaki Akitaka Makiyama Nozomu Machida Hidekazu Hirano Kenro Hirata Hiroki Hara Hiroshi Yabusaki Yoshito Komatsu Kei Muro |
| author_sort | Hisato Kawakami |
| collection | DOAJ |
| description | Nivolumab (NIVO) plus low-dose ipilimumab (IPI) has shown a promising survival benefit in first-line treatment of microsatellite instability-high (MSI-H) colorectal cancer. We hypothesized that this regimen might also be beneficial for MSI-H gastric cancer (GC), which accounts for ~5% of all GC cases. NO LIMIT (WJOG13320G/CA209-7W7) is an investigator-initiated, single-arm, open-label, 14-center phase 2 trial of NIVO plus low-dose IPI for MSI-H GC in the first-line setting. Eligibility criteria include unresectable advanced, recurrent, or metastatic gastric or esophagogastric junction cancer with a histologically confirmed diagnosis of adenocarcinoma; confirmed MSI-H status with the MSI-IVD Kit (FALCO); no prior systemic anticancer therapy; an Eastern Cooperative Oncology Group performance status of 0 or 1; and a measurable lesion per RECIST 1.1. The primary objective of the study is to determine the overall response rate (ORR) for the NIVO+IPI regimen as assessed by blinded independent central review. Secondary end points include progression-free survival, overall survival, duration of response, safety, tolerability, and biomarkers. The number of patients was set at 28 on the basis of the threshold and expected ORR values of 35 and 65%, respectively, with a one-sided alpha error of 0.025 and power of 0.80. Subjects will receive treatment with nivolumab (240 mg) biweekly in combination with ipilimumab (1 mg/kg) every 6 weeks. The results of this study should clarify the therapeutic potential of NIVO+IPI for MSI-H GC in the first-line setting. Trial registration: JapicCTI-205400. |
| first_indexed | 2024-03-09T00:52:09Z |
| format | Article |
| id | doaj.art-11d56b2c1d7c463d84d70b533dcdbe8d |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T00:52:09Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-11d56b2c1d7c463d84d70b533dcdbe8d2023-12-11T17:07:22ZengMDPI AGCancers2072-66942021-02-0113480510.3390/cancers13040805An Investigator-Initiated Phase 2 Study of Nivolumab Plus Low-Dose Ipilimumab as First-Line Therapy for Microsatellite Instability—High Advanced Gastric or Esophagogastric Junction Cancer (NO LIMIT, WJOG13320G/CA209-7W7)Hisato Kawakami0Shuichi Hironaka1Taito Esaki2Kazuaki Chayama3Masahiro Tsuda4Naotoshi Sugimoto5Shigenori Kadowaki6Akitaka Makiyama7Nozomu Machida8Hidekazu Hirano9Kenro Hirata10Hiroki Hara11Hiroshi Yabusaki12Yoshito Komatsu13Kei Muro14Department of Medical Oncology, Faculty of Medicine, Kindai University, Osaka 589-8511, JapanDepartment of Medical Oncology and Hematology, Faculty of Medicine, Oita University, Oita 879-5593, JapanDepartment of Gastrointestinal and Medical Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka 811-1395, JapanDepartment of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Gastroenterological Oncology, Hyogo Cancer Center, Hyogo 673-8558, JapanDepartment of Medical Oncology, Osaka International Cancer Institute, Osaka 541-8567, JapanDepartment of Clinical Oncology, Aichi Cancer Center Hospital, Aichi 464-8681, JapanCancer Center, Gifu University Hospital, Gifu 501-1194, JapanDepartment of Gastroenterology, Kanagawa Cancer Center, Kanagawa 241-8515, JapanGastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo 104-0045, JapanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo 160-8582, JapanDepartment of Gastroenterology, Saitama Cancer Center, Saitama 362-0806, JapanDepartment of Gastroenterological Surgery, Niigata Cancer Center Hospital, Niigata 951-8566, JapanDepartment of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, Hokkaido 060-8648, JapanDepartment of Clinical Oncology, Aichi Cancer Center Hospital, Aichi 464-8681, JapanNivolumab (NIVO) plus low-dose ipilimumab (IPI) has shown a promising survival benefit in first-line treatment of microsatellite instability-high (MSI-H) colorectal cancer. We hypothesized that this regimen might also be beneficial for MSI-H gastric cancer (GC), which accounts for ~5% of all GC cases. NO LIMIT (WJOG13320G/CA209-7W7) is an investigator-initiated, single-arm, open-label, 14-center phase 2 trial of NIVO plus low-dose IPI for MSI-H GC in the first-line setting. Eligibility criteria include unresectable advanced, recurrent, or metastatic gastric or esophagogastric junction cancer with a histologically confirmed diagnosis of adenocarcinoma; confirmed MSI-H status with the MSI-IVD Kit (FALCO); no prior systemic anticancer therapy; an Eastern Cooperative Oncology Group performance status of 0 or 1; and a measurable lesion per RECIST 1.1. The primary objective of the study is to determine the overall response rate (ORR) for the NIVO+IPI regimen as assessed by blinded independent central review. Secondary end points include progression-free survival, overall survival, duration of response, safety, tolerability, and biomarkers. The number of patients was set at 28 on the basis of the threshold and expected ORR values of 35 and 65%, respectively, with a one-sided alpha error of 0.025 and power of 0.80. Subjects will receive treatment with nivolumab (240 mg) biweekly in combination with ipilimumab (1 mg/kg) every 6 weeks. The results of this study should clarify the therapeutic potential of NIVO+IPI for MSI-H GC in the first-line setting. Trial registration: JapicCTI-205400.https://www.mdpi.com/2072-6694/13/4/805gastric cancermicrosatellite instabilitynivolumabipilimumab |
| spellingShingle | Hisato Kawakami Shuichi Hironaka Taito Esaki Kazuaki Chayama Masahiro Tsuda Naotoshi Sugimoto Shigenori Kadowaki Akitaka Makiyama Nozomu Machida Hidekazu Hirano Kenro Hirata Hiroki Hara Hiroshi Yabusaki Yoshito Komatsu Kei Muro An Investigator-Initiated Phase 2 Study of Nivolumab Plus Low-Dose Ipilimumab as First-Line Therapy for Microsatellite Instability—High Advanced Gastric or Esophagogastric Junction Cancer (NO LIMIT, WJOG13320G/CA209-7W7) Cancers gastric cancer microsatellite instability nivolumab ipilimumab |
| title | An Investigator-Initiated Phase 2 Study of Nivolumab Plus Low-Dose Ipilimumab as First-Line Therapy for Microsatellite Instability—High Advanced Gastric or Esophagogastric Junction Cancer (NO LIMIT, WJOG13320G/CA209-7W7) |
| title_full | An Investigator-Initiated Phase 2 Study of Nivolumab Plus Low-Dose Ipilimumab as First-Line Therapy for Microsatellite Instability—High Advanced Gastric or Esophagogastric Junction Cancer (NO LIMIT, WJOG13320G/CA209-7W7) |
| title_fullStr | An Investigator-Initiated Phase 2 Study of Nivolumab Plus Low-Dose Ipilimumab as First-Line Therapy for Microsatellite Instability—High Advanced Gastric or Esophagogastric Junction Cancer (NO LIMIT, WJOG13320G/CA209-7W7) |
| title_full_unstemmed | An Investigator-Initiated Phase 2 Study of Nivolumab Plus Low-Dose Ipilimumab as First-Line Therapy for Microsatellite Instability—High Advanced Gastric or Esophagogastric Junction Cancer (NO LIMIT, WJOG13320G/CA209-7W7) |
| title_short | An Investigator-Initiated Phase 2 Study of Nivolumab Plus Low-Dose Ipilimumab as First-Line Therapy for Microsatellite Instability—High Advanced Gastric or Esophagogastric Junction Cancer (NO LIMIT, WJOG13320G/CA209-7W7) |
| title_sort | investigator initiated phase 2 study of nivolumab plus low dose ipilimumab as first line therapy for microsatellite instability high advanced gastric or esophagogastric junction cancer no limit wjog13320g ca209 7w7 |
| topic | gastric cancer microsatellite instability nivolumab ipilimumab |
| url | https://www.mdpi.com/2072-6694/13/4/805 |
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