Tamrintamab pamozirine (SC-003) in patients with platinum-resistant/refractory ovarian cancer: Findings of a phase 1 study.
Gynecol Oncol
; 158(3): 640-645, 2020 09.
Article
em En
| MEDLINE
| ID: mdl-32513564
ABSTRACT
OBJECTIVE:
Epithelial ovarian carcinoma (EOC) is diagnosed at advanced stage in the majority of women and, despite being initially chemosensitive, eventually recurs and develops resistance to known therapies. SC-003 is a pyrrolobenzodiazepine-based antibody-drug conjugate targeting dipeptidase 3 (DPEP3), a membrane-bound dipeptidase associated with tumor-initiating cells in patient-derived EOC xenograft models. This first-in-human phase 1a/1b study evaluated the safety/tolerability, pharmacokinetics, and preliminary antitumor activity of SC-003 alone or in combination with budigalimab (formerly ABBV-181), an antibody targeting PD-1, in patients with platinum-resistant/refractory EOC (NCT02539719).METHODS:
Patients received SC-003 at 1 of 6 dose levels (0.025-0.4â¯mg/kg) every 3â¯weeks (Q3W), utilizing a standard 3â¯+â¯3 design (dose-limiting toxicity [DLT] period 21â¯days). Patients with DPEP3-positive tumors were enrolled in the dose-expansion phase of the study and treated with SC-003 monotherapy or in combination with budigalimab.RESULTS:
Seventy-four patients (nâ¯=â¯29, dose escalation; nâ¯=â¯45, dose expansion; nâ¯=â¯3 budigalimab combination) were enrolled and received ≥1 dose of study drug. One DLT occurred (grade 3 ileus) but was considered unrelated to study drug. The MTD for the Q3W schedule was 0.3â¯mg/kg and the SC-003 doses selected for the dose-expansion phase of the study were 0.3â¯mg/kg and 0.2â¯mg/kg. The most common treatment-emergent adverse events were fatigue, nausea, decreased appetite, pleural effusion, abdominal pain, and peripheral edema. The overall response rate was low (4%), and responses were not durable. Post-hoc examination of antitumor activity suggested a higher response rate in patients with higher DPEP3 expression.CONCLUSIONS:
SC-003 lacked the requisite safety profile and antitumor activity to warrant further development.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Pirróis
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Benzodiazepinas
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Imunoconjugados
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Carcinoma Epitelial do Ovário
Tipo de estudo:
Clinical_trials
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Diagnostic_studies
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Prognostic_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article