Regorafenib plus sintilimab as a salvage treatment for microsatellite stable metastatic colorectal cancer: a single-arm, open-label, phase II clinical trial
Abstract Immune checkpoint inhibitors (ICIs) have limited efficacy in microsatellite stable (MSS) metastatic colorectal cancer (mCRC), and combination therapy needs to be further explored. In this single-arm, open-label, phase II trial (NCT04745130), we evaluate the efficacy and safety of the combin...
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56748-3 |
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| author | Rui Liu Zhi Ji Xia Wang Lila Zhu Jiaqi Xin Lijun Ma Jiayu Zhang Shaohua Ge Le Zhang Yuchong Yang Tao Ning Ming Bai Jingjing Duan Feixue Wang Yansha Sun Hongli Li Ting Deng Yi Ba Jihui Hao |
| author_facet | Rui Liu Zhi Ji Xia Wang Lila Zhu Jiaqi Xin Lijun Ma Jiayu Zhang Shaohua Ge Le Zhang Yuchong Yang Tao Ning Ming Bai Jingjing Duan Feixue Wang Yansha Sun Hongli Li Ting Deng Yi Ba Jihui Hao |
| author_sort | Rui Liu |
| collection | DOAJ |
| description | Abstract Immune checkpoint inhibitors (ICIs) have limited efficacy in microsatellite stable (MSS) metastatic colorectal cancer (mCRC), and combination therapy needs to be further explored. In this single-arm, open-label, phase II trial (NCT04745130), we evaluate the efficacy and safety of the combination therapy of antiangiogenesis (regorafenib) and ICI (sintilimab) in patients with MSS mCRC. The primary endpoint is overall survival (OS). Secondary endpoints include progression free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and safety. The median OS and PFS are 14.1 months (95% CI: 10.5–17.7) and 4.1 months (95% CI: 3.4–4.8), respectively. The ORR is 21.4%, DCR is 63.1%, and DoR is 13.0 months (95% CI: 2.5–23.5). Patients with RAS/RAF wild-type exhibit significantly longer median OS (23.3 months, 95% CI: 10.0–36.6) compared to those with mutations (12.1 months, 95% CI: 8.4–15.8). The combination therapy is well tolerated and has limited toxicity. Biomarker analysis, including transcriptome sequencing and multiplex immunohistochemistry staining are performed. The efficacy of this combination treatment is tied to specific gene expressions governing tumor metabolism. Moreover, the effectiveness of immunotherapy depends on the abundance of immune cells, as well as the distance between immune cells and tumor cells. |
| format | Article |
| id | doaj-art-e63d542dc5144bcb97d8bac0b15bf089 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-e63d542dc5144bcb97d8bac0b15bf0892025-08-20T03:00:59ZengNature PortfolioNature Communications2041-17232025-02-0116111410.1038/s41467-025-56748-3Regorafenib plus sintilimab as a salvage treatment for microsatellite stable metastatic colorectal cancer: a single-arm, open-label, phase II clinical trialRui Liu0Zhi Ji1Xia Wang2Lila Zhu3Jiaqi Xin4Lijun Ma5Jiayu Zhang6Shaohua Ge7Le Zhang8Yuchong Yang9Tao Ning10Ming Bai11Jingjing Duan12Feixue Wang13Yansha Sun14Hongli Li15Ting Deng16Yi Ba17Jihui Hao18Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive CancerAbstract Immune checkpoint inhibitors (ICIs) have limited efficacy in microsatellite stable (MSS) metastatic colorectal cancer (mCRC), and combination therapy needs to be further explored. In this single-arm, open-label, phase II trial (NCT04745130), we evaluate the efficacy and safety of the combination therapy of antiangiogenesis (regorafenib) and ICI (sintilimab) in patients with MSS mCRC. The primary endpoint is overall survival (OS). Secondary endpoints include progression free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and safety. The median OS and PFS are 14.1 months (95% CI: 10.5–17.7) and 4.1 months (95% CI: 3.4–4.8), respectively. The ORR is 21.4%, DCR is 63.1%, and DoR is 13.0 months (95% CI: 2.5–23.5). Patients with RAS/RAF wild-type exhibit significantly longer median OS (23.3 months, 95% CI: 10.0–36.6) compared to those with mutations (12.1 months, 95% CI: 8.4–15.8). The combination therapy is well tolerated and has limited toxicity. Biomarker analysis, including transcriptome sequencing and multiplex immunohistochemistry staining are performed. The efficacy of this combination treatment is tied to specific gene expressions governing tumor metabolism. Moreover, the effectiveness of immunotherapy depends on the abundance of immune cells, as well as the distance between immune cells and tumor cells.https://doi.org/10.1038/s41467-025-56748-3 |
| spellingShingle | Rui Liu Zhi Ji Xia Wang Lila Zhu Jiaqi Xin Lijun Ma Jiayu Zhang Shaohua Ge Le Zhang Yuchong Yang Tao Ning Ming Bai Jingjing Duan Feixue Wang Yansha Sun Hongli Li Ting Deng Yi Ba Jihui Hao Regorafenib plus sintilimab as a salvage treatment for microsatellite stable metastatic colorectal cancer: a single-arm, open-label, phase II clinical trial Nature Communications |
| title | Regorafenib plus sintilimab as a salvage treatment for microsatellite stable metastatic colorectal cancer: a single-arm, open-label, phase II clinical trial |
| title_full | Regorafenib plus sintilimab as a salvage treatment for microsatellite stable metastatic colorectal cancer: a single-arm, open-label, phase II clinical trial |
| title_fullStr | Regorafenib plus sintilimab as a salvage treatment for microsatellite stable metastatic colorectal cancer: a single-arm, open-label, phase II clinical trial |
| title_full_unstemmed | Regorafenib plus sintilimab as a salvage treatment for microsatellite stable metastatic colorectal cancer: a single-arm, open-label, phase II clinical trial |
| title_short | Regorafenib plus sintilimab as a salvage treatment for microsatellite stable metastatic colorectal cancer: a single-arm, open-label, phase II clinical trial |
| title_sort | regorafenib plus sintilimab as a salvage treatment for microsatellite stable metastatic colorectal cancer a single arm open label phase ii clinical trial |
| url | https://doi.org/10.1038/s41467-025-56748-3 |
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