dc.contributor
Institut Català de la Salut
dc.contributor
[Santin AD] Yale School of Medicine, New Haven, CT, USA. [Vergote I] University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium. [González-Martín A] Clinica Universidad de Navarra, Madrid, Spain. [Moore K] University of Oklahoma Health Sciences Center, Oklahoma, OK, USA. [Oaknin A] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Romero I] Instituto Valenciano de Oncología, Valencia, Spain
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Santin, Alessandro
dc.contributor.author
González-Martin, Antonio
dc.contributor.author
Moore, Kathleen N
dc.contributor.author
Oaknin Benzaquen, Ana Mazaltob
dc.contributor.author
Romero, Ignacio
dc.contributor.author
Vergote, Ignace
dc.date.accessioned
2025-10-25T05:37:08Z
dc.date.available
2025-10-25T05:37:08Z
dc.date.issued
2023-04-20T09:38:28Z
dc.date.issued
2023-04-20T09:38:28Z
dc.identifier
Santin AD, Vergote I, González-Martín A, Moore K, Oaknin A, Romero I, et al. Safety and activity of anti-mesothelin antibody–drug conjugate anetumab ravtansine in combination with pegylated-liposomal doxorubicin in platinum-resistant ovarian cancer: multicenter, phase Ib dose escalation and expansion study. Int J Gynecol Cancer. 2023 Apr;33(4):562–70.
dc.identifier
https://hdl.handle.net/11351/9375
dc.identifier
10.1136/ijgc-2022-003927
dc.identifier
000904327300001
dc.identifier.uri
http://hdl.handle.net/11351/9375
dc.description.abstract
Ovarian cancer
dc.description.abstract
Càncer d'ovari
dc.description.abstract
Cáncer de ovario
dc.description.abstract
Objectives Anetumab ravtansine is an antibody-drug conjugate consisting of a fully human anti-mesothelin monoclonal antibody conjugated to cytotoxic maytansinoid tubulin inhibitor DM4. Mesothelin is highly expressed in ovarian cancer. This phase Ib study determines the safety, pharmacokinetics, and anti-tumor activity of anetumab ravtansine and pegylated liposomal doxorubicin in mesothelin-expressing platinum-resistant ovarian cancer.
Methods Anetumab ravtansine (5.5 or 6.5 mg/kg) and pegylated liposomal doxorubicin (30 mg/m2) were administered intravenously every 3 weeks to 65 patients with platinum-resistant epithelial ovarian cancer. Mesothelin expression was assessed by central immunohistochemistry. Adverse events, tumor response (RECIST 1.1), and progression-free survival were determined. Biomarker samples were assessed by ELISA and next-generation sequencing.
Results In dose escalation, nine patients received anetumab ravtansine across two doses (5.5 or 6.5 mg/kg). The maximum tolerated dose of anetumab ravtansine was 6.5 mg/kg every 3 weeks and no dose-limiting toxicities were observed. In dose expansion, 56 patients were treated at the maximum tolerated dose. The most common treatment-emergent adverse events of any grade were nausea (47.7%), decreased appetite (43.1%), fatigue (38.5%), diarrhea (32.3%), and corneal disorder (29.2%). In all treated patients the objective response rate was 27.7% (95% CI 17.3% to 40.2%), including one complete (1.5%) and 17 partial responses (26.2%), with median duration of response of 7.6 (95% CI 3.3 to 10.2) months and median progression-free survival of 5.0 (95% CI 3.2 to 6.0) months. In an exploratory analysis of a sub-set of patients (n=19) with high mesothelin expression who received ≤3 prior lines of systemic therapy, the objective response rate was 42.1% (95% CI 20.3% to 66.5%) with a median duration of response of 8.3 (95% CI 4.1 to 12.0) months and median progression-free survival of 8.5 (95% CI 4.0 to 11.4) months.
Conclusions Anetumab ravtansine and pegylated liposomal doxorubicin showed tolerability and promising clinical activity. These results established the dose schedule and the mesothelin-positive target population of this combination for a phase III study in platinum-resistant ovarian cancer.
dc.description.abstract
This study was funded by Bayer AG.
dc.format
application/pdf
dc.relation
International Journal of Gynecological Cancer;33(4)
dc.relation
http://dx.doi.org/10.1136/ijgc-2022-003927
dc.rights
Attribution-NonCommercial 4.0 International
dc.rights
http://creativecommons.org/licenses/by-nc/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Ovaris - Càncer - Tractament
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Medicaments antineoplàstics - Ús terapèutic
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Anticossos monoclonals - Ús terapèutic
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DISEASES::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms
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Other subheadings::Other subheadings::Other subheadings::/drug therapy
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ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols
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CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Serum Globulins::Immunoglobulins::Antibodies::Immunoconjugates
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ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas
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Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
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TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada
dc.subject
COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::globulinas séricas::inmunoglobulinas::anticuerpos::inmunoconjugados
dc.title
Safety and activity of anti-mesothelin antibody–drug conjugate anetumab ravtansine in combination with pegylated-liposomal doxorubicin in platinum-resistant ovarian cancer: multicenter, phase Ib dose escalation and expansion study
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
