Phase Ib Study of Navicixizumab Plus Paclitaxel in Patients With Platinum-Resistant Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
PURPOSE: This phase Ib study evaluated the safety and efficacy of paclitaxel plus navicixizumab, a bispecific antiangiogenic antibody to vascular endothelial growth factor and delta-like ligand 4, against platinum-resistant ovarian cancer.
PATIENTS AND METHODS: This open-label, nonrandomized, dose-escalation and -expansion study included 44 patients with previously treated, recurrent, platinum-resistant grade 2/3 ovarian cancer. Treatment was intravenous navicixizumab (3 mg/kg or 4 mg/kg once every 2 weeks) plus paclitaxel (80 mg/m2 intravenously on days 0, 7, and 14 of 28-day cycles). The primary and secondary objectives were to evaluate the safety and efficacy of navicixizumab plus paclitaxel. An RNA-based diagnostic panel was retrospectively used to test the hypothesis that tumors with high angiogenesis or immune-suppressed tumor microenvironment (TME) subtypes (biomarker-positive) are more likely to respond to navicixizumab than those with immune-active/-desert TME subtypes (biomarker-negative). RNA expression was analyzed in available pretreatment tumor tissue to classify 33 patients' TME subtypes, and TME panel findings were correlated with tumor response.
RESULTS: The dose-escalation cohorts enrolled patients at navicixizumab doses of 3 mg/kg once every 2 weeks (n = 3) and 4 mg/kg once every 2 weeks (n = 2); 3 mg/kg was selected for expansion (n = 39). No dose-limiting toxicities occurred. The most common grade 3/4 treatment-related adverse events were hypertension (40.9%), neutropenia (6.8%), and thrombocytopenia (4.5%). Pulmonary hypertension occurred in 18.2% (grade 1-2). The overall objective response rate was 43.2% (95% CI, 28.3 to 59.0): 33.3% (95% CI, 17.3 to 52.8) in patients previously treated with bevacizumab, 64.3% (95% CI, 35.1 to 87.2) in bevacizumab-naive patients, and 62% (95% CI, 31.6 to 86.1) in biomarker-positive patients. The median duration of response was 6 months (95% CI, 5.4 months to not estimable).
CONCLUSION: Navicixizumab plus paclitaxel demonstrated promising clinical activity in bevacizumab-treated and -naive patients with platinum-resistant ovarian cancer, with manageable toxicity.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:40 |
|---|---|
| Enthalten in: |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology - 40(2022), 23 vom: 10. Aug., Seite 2568-2577 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fu, Siqing [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 09.08.2022 Date Revised 13.10.2022 published: Print-Electronic ClinicalTrials.gov: NCT03030287 Citation Status MEDLINE |
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| doi: |
10.1200/JCO.21.01801 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM339683333 |
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| 245 | 1 | 0 | |a Phase Ib Study of Navicixizumab Plus Paclitaxel in Patients With Platinum-Resistant Ovarian, Primary Peritoneal, or Fallopian Tube Cancer |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Completed 09.08.2022 | ||
| 500 | |a Date Revised 13.10.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT03030287 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a PURPOSE: This phase Ib study evaluated the safety and efficacy of paclitaxel plus navicixizumab, a bispecific antiangiogenic antibody to vascular endothelial growth factor and delta-like ligand 4, against platinum-resistant ovarian cancer | ||
| 520 | |a PATIENTS AND METHODS: This open-label, nonrandomized, dose-escalation and -expansion study included 44 patients with previously treated, recurrent, platinum-resistant grade 2/3 ovarian cancer. Treatment was intravenous navicixizumab (3 mg/kg or 4 mg/kg once every 2 weeks) plus paclitaxel (80 mg/m2 intravenously on days 0, 7, and 14 of 28-day cycles). The primary and secondary objectives were to evaluate the safety and efficacy of navicixizumab plus paclitaxel. An RNA-based diagnostic panel was retrospectively used to test the hypothesis that tumors with high angiogenesis or immune-suppressed tumor microenvironment (TME) subtypes (biomarker-positive) are more likely to respond to navicixizumab than those with immune-active/-desert TME subtypes (biomarker-negative). RNA expression was analyzed in available pretreatment tumor tissue to classify 33 patients' TME subtypes, and TME panel findings were correlated with tumor response | ||
| 520 | |a RESULTS: The dose-escalation cohorts enrolled patients at navicixizumab doses of 3 mg/kg once every 2 weeks (n = 3) and 4 mg/kg once every 2 weeks (n = 2); 3 mg/kg was selected for expansion (n = 39). No dose-limiting toxicities occurred. The most common grade 3/4 treatment-related adverse events were hypertension (40.9%), neutropenia (6.8%), and thrombocytopenia (4.5%). Pulmonary hypertension occurred in 18.2% (grade 1-2). The overall objective response rate was 43.2% (95% CI, 28.3 to 59.0): 33.3% (95% CI, 17.3 to 52.8) in patients previously treated with bevacizumab, 64.3% (95% CI, 35.1 to 87.2) in bevacizumab-naive patients, and 62% (95% CI, 31.6 to 86.1) in biomarker-positive patients. The median duration of response was 6 months (95% CI, 5.4 months to not estimable) | ||
| 520 | |a CONCLUSION: Navicixizumab plus paclitaxel demonstrated promising clinical activity in bevacizumab-treated and -naive patients with platinum-resistant ovarian cancer, with manageable toxicity | ||
| 650 | 4 | |a Clinical Trial, Phase I | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Corr, Bradley R |e verfasserin |4 aut | |
| 700 | 1 | |a Culm-Merdek, Kerry |e verfasserin |4 aut | |
| 700 | 1 | |a Mockbee, Colleen |e verfasserin |4 aut | |
| 700 | 1 | |a Youssoufian, Hagop |e verfasserin |4 aut | |
| 700 | 1 | |a Stagg, Robert |e verfasserin |4 aut | |
| 700 | 1 | |a Naumann, R Wendel |e verfasserin |4 aut | |
| 700 | 1 | |a Wenham, Robert M |e verfasserin |4 aut | |
| 700 | 1 | |a Rosengarten, Rafael D |e verfasserin |4 aut | |
| 700 | 1 | |a Benjamin, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Hamilton, Erika Paige |e verfasserin |4 aut | |
| 700 | 1 | |a Moore, Kathleen N |e verfasserin |4 aut | |
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