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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
- Source :
- Scientia
- Publication Year :
- 2022
- Publisher :
- BMJ, 2022.
-
Abstract
- ObjectivesAnetumab 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.MethodsAnetumab 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.ResultsIn 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.ConclusionsAnetumab 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.Trial registration numberNCT02751918.
- Subjects :
- Science & Technology
Anticossos monoclonals - Ús terapèutic
Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms [DISEASES]
BEVACIZUMAB
terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS]
Medicaments antineoplàstics - Ús terapèutic
Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores]
Obstetrics & Gynecology
Obstetrics and Gynecology
aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::globulinas séricas::inmunoglobulinas::anticuerpos::inmunoconjugados [COMPUESTOS QUÍMICOS Y DROGAS]
Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Serum Globulins::Immunoglobulins::Antibodies::Immunoconjugates [CHEMICALS AND DRUGS]
Ovaris - Càncer - Tractament
neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas [ENFERMEDADES]
CHEMOTHERAPY
Other subheadings::Other subheadings::/drug therapy [Other subheadings]
ovarian cancer
Oncology
Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT]
TRIAL
WEEKLY PACLITAXEL
TOPOTECAN
Life Sciences & Biomedicine
Subjects
Details
- ISSN :
- 15251438 and 1048891X
- Volume :
- 33
- Database :
- OpenAIRE
- Journal :
- International Journal of Gynecologic Cancer
- Accession number :
- edsair.doi.dedup.....15a0c0b8ed9cef8add723b9465b06491