Phase 1b study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate, in combination with carboplatin and bevacizumab in patients with platinum-sensitive ovarian cancer
Copyright © 2024. Published by Elsevier Inc..
OBJECTIVE: Evaluate the antitumor activity and safety profile of the triplet combination of mirvetuximab soravtansine (MIRV), carboplatin, and bevacizumab in recurrent, platinum-sensitive ovarian cancer.
METHODS: Participants with recurrent, platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer (1-2 prior lines of therapy) received MIRV (6 mg/kg adjusted ideal body weight), carboplatin (AUC5), and bevacizumab (15 mg/kg) once every 3 weeks. Carboplatin could be discontinued after 6 cycles per investigator discretion; continuation of MIRV+bevacizumab as maintenance therapy was permitted. Eligibility included folate receptor alpha (FRα) expression by immunohistochemistry (≥50% of cells with ≥2+ intensity; PS2+ scoring); prior bevacizumab was allowed. Tumor response, duration of response (DOR), progression-free survival (PFS), and adverse events (AEs) were assessed.
RESULTS: Forty-one participants received triplet therapy, with a median of 6, 12, and 13 cycles of carboplatin, MIRV, and bevacizumab, respectively. The confirmed objective response rate was 83% (9 complete and 25 partial responses). The median DOR was 10.9 months; median PFS was 13.5 months. AEs (any grade) occurred as expected, based on each agent's safety profile; most common were diarrhea (83%), nausea (76%), fatigue (73%), thrombocytopenia (71%), and blurred vision (68%). Most cases were mild to moderate (grade ≤2), except for thrombocytopenia, for which most drug-related discontinuations occurred, and neutropenia.
CONCLUSIONS: This triplet regimen (MIRV+carboplatin+bevacizumab) was highly active, with a tolerable AE profile in participants with recurrent, platinum-sensitive, FRα-expressing ovarian cancer. Thrombocytopenia was the primary cause of dose modifications. These outcomes compare favorably to historical data reported for platinum-based chemotherapy plus bevacizumab regimens in similar patient populations.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:185 |
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| Enthalten in: |
Gynecologic oncology - 185(2024) vom: 05. März, Seite 186-193 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Richardson, Debra L [VerfasserIn] |
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| Links: |
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| Themen: |
Antibody-drug conjugate |
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| Anmerkungen: |
Date Revised 06.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1016/j.ygyno.2024.01.045 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369371038 |
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| 041 | |a eng | ||
| 100 | 1 | |a Richardson, Debra L |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Phase 1b study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate, in combination with carboplatin and bevacizumab in patients with platinum-sensitive ovarian cancer |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Revised 06.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a Copyright © 2024. Published by Elsevier Inc. | ||
| 520 | |a OBJECTIVE: Evaluate the antitumor activity and safety profile of the triplet combination of mirvetuximab soravtansine (MIRV), carboplatin, and bevacizumab in recurrent, platinum-sensitive ovarian cancer | ||
| 520 | |a METHODS: Participants with recurrent, platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer (1-2 prior lines of therapy) received MIRV (6 mg/kg adjusted ideal body weight), carboplatin (AUC5), and bevacizumab (15 mg/kg) once every 3 weeks. Carboplatin could be discontinued after 6 cycles per investigator discretion; continuation of MIRV+bevacizumab as maintenance therapy was permitted. Eligibility included folate receptor alpha (FRα) expression by immunohistochemistry (≥50% of cells with ≥2+ intensity; PS2+ scoring); prior bevacizumab was allowed. Tumor response, duration of response (DOR), progression-free survival (PFS), and adverse events (AEs) were assessed | ||
| 520 | |a RESULTS: Forty-one participants received triplet therapy, with a median of 6, 12, and 13 cycles of carboplatin, MIRV, and bevacizumab, respectively. The confirmed objective response rate was 83% (9 complete and 25 partial responses). The median DOR was 10.9 months; median PFS was 13.5 months. AEs (any grade) occurred as expected, based on each agent's safety profile; most common were diarrhea (83%), nausea (76%), fatigue (73%), thrombocytopenia (71%), and blurred vision (68%). Most cases were mild to moderate (grade ≤2), except for thrombocytopenia, for which most drug-related discontinuations occurred, and neutropenia | ||
| 520 | |a CONCLUSIONS: This triplet regimen (MIRV+carboplatin+bevacizumab) was highly active, with a tolerable AE profile in participants with recurrent, platinum-sensitive, FRα-expressing ovarian cancer. Thrombocytopenia was the primary cause of dose modifications. These outcomes compare favorably to historical data reported for platinum-based chemotherapy plus bevacizumab regimens in similar patient populations | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Antibody-drug conjugate | |
| 650 | 4 | |a Clinical trial | |
| 650 | 4 | |a Combination therapy | |
| 650 | 4 | |a Folate receptor alpha | |
| 650 | 4 | |a Mirvetuximab soravtansine | |
| 650 | 4 | |a Platinum-sensitive ovarian cancer | |
| 700 | 1 | |a Moore, Kathleen N |e verfasserin |4 aut | |
| 700 | 1 | |a Vergote, Ignace |e verfasserin |4 aut | |
| 700 | 1 | |a Gilbert, Lucy |e verfasserin |4 aut | |
| 700 | 1 | |a Martin, Lainie P |e verfasserin |4 aut | |
| 700 | 1 | |a Mantia-Smaldone, Gina M |e verfasserin |4 aut | |
| 700 | 1 | |a Castro, Cesar M |e verfasserin |4 aut | |
| 700 | 1 | |a Provencher, Diane |e verfasserin |4 aut | |
| 700 | 1 | |a Matulonis, Ursula A |e verfasserin |4 aut | |
| 700 | 1 | |a Stec, James |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yuemei |e verfasserin |4 aut | |
| 700 | 1 | |a Method, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a O'Malley, David M |e verfasserin |4 aut | |
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