Phase 1b study of anti-NaPi2b antibody-drug conjugate lifastuzumab vedotin (DNIB0600A) in patients with platinum-sensitive recurrent ovarian cancer.
Gynecol Oncol
; 158(3): 631-639, 2020 09.
Article
em En
| MEDLINE
| ID: mdl-32534811
ABSTRACT
OBJECTIVE:
This study investigated the safety and tolerability of lifastuzumab vedotin (DNIB0600A) (LIFA), an antibody-drug conjugate, in patients with recurrent platinum-sensitive ovarian cancer (PSOC).METHODS:
In this open-label, multicenter phase 1b study, LIFA was administered intravenously once every 3 weeks (Q3W) with starting dose 1.2 mg/kg in a 3 + 3 dose-escalation scheme. All patients received carboplatin at dose AUC 6 mg/mL·min (AUC6) Q3W for up to 6 cycles. Dose expansion cohorts were enrolled ± bevacizumab 15 mg/kg Q3W.RESULTS:
Patients received LIFA at 1.2, 1.8, and 2.4 mg (n = 4, 5, and 20, respectively) with carboplatin. The maximum tolerated dose was not reached. The recommended phase 2 dose (RP2D) was LIFA 2.4 mg/kg + carboplatin AUC6 (cycles 1-6), with or without bevacizumab 15 mg/kg. Twelve patients received RP2D with bevacizumab. All patients experienced ≥1 adverse event (AE). The most common treatment-related AEs were neutropenia, peripheral neuropathy, thrombocytopenia, nausea, fatigue, anemia, diarrhea, vomiting, hypomagnesaemia, aspartate aminotransferase increased, alanine aminotransferase increased, and alopecia. Thirty-four (83%) patients experienced grade ≥ 3 AEs, the most frequent of which were neutropenia and thrombocytopenia. Nine (22%) patients experienced serious AEs. Pulmonary toxicities (34%), considered a potential risk of LIFA, included one patient who discontinued study treatment due to grade 2 pneumonitis. The median duration of progression-free survival was 10.71 months (95% CI 8.54, 13.86) with confirmed complete/partial responses in 24 (59%) patients. Pharmacokinetics of mono-therapy LIFA was similar in combination therapy.CONCLUSION:
LIFA in combination with carboplatin ± bevacizumab demonstrated acceptable safety and encouraging activity in PSOC patients.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Protocolos de Quimioterapia Combinada Antineoplásica
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Anticorpos Monoclonais Humanizados
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Carcinoma Epitelial do Ovário
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Recidiva Local de Neoplasia
Tipo de estudo:
Clinical_trials
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Diagnostic_studies
Limite:
Aged
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Aged80
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Gynecol Oncol
Ano de publicação:
2020
Tipo de documento:
Article