First-line camrelizumab (a PD-1 inhibitor) plus apatinib (an VEGFR-2 inhibitor) and chemotherapy for advanced gastric cancer (SPACE) : a phase 1 study
© 2024. The Author(s)..
Patients with advanced gastric cancer typically face a grim prognosis. This phase 1a (dose escalation) and phase 1b (dose expansion) study investigated safety and efficacy of first-line camrelizumab plus apatinib and chemotherapy for advanced gastric or gastroesophageal junction adenocarcinoma. The primary endpoints included maximum tolerated dose (MTD) in phase 1a and objective response rate (ORR) across phase 1a and 1b. Phase 1a tested three dose regimens of camrelizumab, apatinib, oxaliplatin, and S-1. Dose regimen 1: camrelizumab 200 mg on day 1, apatinib 250 mg every other day, oxaliplatin 100 mg/m² on day 1, and S-1 40 mg twice a day on days 1-14. Dose regimen 2: same as dose regimen 1, but oxaliplatin 130 mg/m². Dose regimen 3: same as dose regimen 2, but apatinib 250 mg daily. Thirty-four patients were included (9 in phase 1a, 25 in phase 1b). No dose-limiting toxicities occurred so no MTD was identified. Dose 3 was set for the recommended phase 2 doses and administered in phase 1b. The confirmed ORR was 76.5% (95% CI 58.8-89.3). The median progression-free survival was 8.4 months (95% CI 5.9-not evaluable [NE]), and the median overall survival (OS) was not mature (11.6-NE). Ten patients underwent surgery after treatment and the multidisciplinary team evaluation. Among 24 patients without surgery, the median OS was 19.6 months (7.8-NE). Eighteen patients (52.9%) developed grade ≥ 3 treatment-emergent adverse events. Camrelizumab plus apatinib and chemotherapy showed favorable clinical outcomes and manageable safety for untreated advanced gastric cancer (ChiCTR2000034109).
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
|---|---|
| Enthalten in: |
Signal transduction and targeted therapy - 9(2024), 1 vom: 25. März, Seite 73 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Chen, Xiaofeng [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 27.03.2024 Date Revised 05.04.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41392-024-01773-9 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM37017609X |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM37017609X | ||
| 003 | DE-627 | ||
| 005 | 20240405233952.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240327s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41392-024-01773-9 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1366.xml |
| 035 | |a (DE-627)NLM37017609X | ||
| 035 | |a (NLM)38528050 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Chen, Xiaofeng |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a First-line camrelizumab (a PD-1 inhibitor) plus apatinib (an VEGFR-2 inhibitor) and chemotherapy for advanced gastric cancer (SPACE) |b a phase 1 study |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 27.03.2024 | ||
| 500 | |a Date Revised 05.04.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a Patients with advanced gastric cancer typically face a grim prognosis. This phase 1a (dose escalation) and phase 1b (dose expansion) study investigated safety and efficacy of first-line camrelizumab plus apatinib and chemotherapy for advanced gastric or gastroesophageal junction adenocarcinoma. The primary endpoints included maximum tolerated dose (MTD) in phase 1a and objective response rate (ORR) across phase 1a and 1b. Phase 1a tested three dose regimens of camrelizumab, apatinib, oxaliplatin, and S-1. Dose regimen 1: camrelizumab 200 mg on day 1, apatinib 250 mg every other day, oxaliplatin 100 mg/m² on day 1, and S-1 40 mg twice a day on days 1-14. Dose regimen 2: same as dose regimen 1, but oxaliplatin 130 mg/m². Dose regimen 3: same as dose regimen 2, but apatinib 250 mg daily. Thirty-four patients were included (9 in phase 1a, 25 in phase 1b). No dose-limiting toxicities occurred so no MTD was identified. Dose 3 was set for the recommended phase 2 doses and administered in phase 1b. The confirmed ORR was 76.5% (95% CI 58.8-89.3). The median progression-free survival was 8.4 months (95% CI 5.9-not evaluable [NE]), and the median overall survival (OS) was not mature (11.6-NE). Ten patients underwent surgery after treatment and the multidisciplinary team evaluation. Among 24 patients without surgery, the median OS was 19.6 months (7.8-NE). Eighteen patients (52.9%) developed grade ≥ 3 treatment-emergent adverse events. Camrelizumab plus apatinib and chemotherapy showed favorable clinical outcomes and manageable safety for untreated advanced gastric cancer (ChiCTR2000034109) | ||
| 650 | 4 | |a Clinical Trial, Phase I | |
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 650 | 7 | |a apatinib |2 NLM | |
| 650 | 7 | |a 5S371K6132 |2 NLM | |
| 650 | 7 | |a camrelizumab |2 NLM | |
| 650 | 7 | |a 73096E137E |2 NLM | |
| 650 | 7 | |a Immune Checkpoint Inhibitors |2 NLM | |
| 650 | 7 | |a Oxaliplatin |2 NLM | |
| 650 | 7 | |a 04ZR38536J |2 NLM | |
| 650 | 7 | |a Pyridines |2 NLM | |
| 650 | 7 | |a Vascular Endothelial Growth Factor Receptor-2 |2 NLM | |
| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 700 | 1 | |a Xu, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xiaobing |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Tongpeng |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Yitong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Deqiang |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Fen |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Kangxin |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Guangfu |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xiao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Rong |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Fengyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Yongbin |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Fang, Yueyu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Liang |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Meng, Lijuan |e verfasserin |4 aut | |
| 700 | 1 | |a Hou, Zhiguo |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Rongrong |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Guan, Ni |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Bei |e verfasserin |4 aut | |
| 700 | 1 | |a Tong, Shuang |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Shiqing |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xing |e verfasserin |4 aut | |
| 700 | 1 | |a Shu, Yongqian |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Signal transduction and targeted therapy |d 2016 |g 9(2024), 1 vom: 25. März, Seite 73 |w (DE-627)NLM257871861 |x 2059-3635 |7 nnns |
| 773 | 1 | 8 | |g volume:9 |g year:2024 |g number:1 |g day:25 |g month:03 |g pages:73 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41392-024-01773-9 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 9 |j 2024 |e 1 |b 25 |c 03 |h 73 | ||