A phase 1 trial of SGN-CD70A in patients with CD70-positive diffuse large B cell lymphoma and mantle cell lymphoma

Autor: Hong Li, David Smith, Thomas E. Boyd, Paul M. Barr, Cindy Yu, Anne Sophie Carret, Steven I. Park, Robert T. Chen, Kathryn S. Kolibaba, Saurabh Chhabra, Tycel Phillips, Edwin C. Kingsley, Paolo Caimi, Elaina M. Gartner
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
Immunoconjugates
CD70 antigen
Lymphoma
Mantle-Cell
Gastroenterology
Benzodiazepines
0302 clinical medicine
hemic and lymphatic diseases
Phase I Studies
Grade 3b Follicular Lymphoma
Pyrrolobenzodiazepine dimer (PBD)
Pharmacology (medical)
Tissue Distribution
Aged
80 and over
Antibodies
Monoclonal
Diffuse
large B cell
lymphoma (DLBCL)
Middle Aged
Prognosis
Gene Expression Regulation
Neoplastic
Mantle-cell lymphoma
Oncology
030220 oncology & carcinogenesis
Female
Lymphoma
Large B-Cell
Diffuse
medicine.symptom
Adult
medicine.medical_specialty
Lymphoma
B-Cell
Maximum Tolerated Dose
Anemia
Nausea
03 medical and health sciences
Refractory
Internal medicine
medicine
Biomarkers
Tumor
Humans
Pyrroles
Adverse effect
Antibody-drug conjugate
Aged
Pharmacology
Salvage Therapy
business.industry
medicine.disease
Grade 3 follicular lymphoma
Lymphoma
030104 developmental biology
Drug Resistance
Neoplasm
Mantle cell lymphoma
Neoplasm Recurrence
Local
business
Diffuse large B-cell lymphoma
CD27 Ligand
Follow-Up Studies
Zdroj: Investigational New Drugs
ISSN: 1573-0646
0167-6997
Popis: Summary Purpose This first-in-human study evaluated SGN-CD70A, an antibody-drug conjugate (ADC) directed against the integral plasma membrane protein CD70 and linked to a pyrrolobenzodiazepine (PBD) dimer, in patients with relapsed or refractory (R/R) CD70-positive non-Hodgkin lymphoma (NHL) including diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and Grade 3b follicular lymphoma (FL3b). Methods SGN-CD70A was administered intravenously on Day 1 of 3-week cycles beginning at 8 mcg/kg with planned dose escalation to 200 mcg/kg. Due to observations of prolonged thrombocytopenia, the study was amended to dose every 6 weeks (q6wk). Results Twenty patients were enrolled and treated with SGN-CD70A. The maximum tolerated dose of SGN-CD70A was 30 mcg/kg q6wk. The most common adverse events (AEs) reported were thrombocytopenia (75%), nausea (55%), anemia (50%), and fatigue (50%). The onset for treatment-related thrombocytopenia typically occurred during Cycle 1. Most of the treatment-related events of thrombocytopenia were ≥ Grade 3. Antitumor activity in patients included 1 complete remission (CR) and 3 partial remissions (PRs), 2 of which were ongoing for at least 42.9 weeks. SGN-CD70A exposures were approximately dose proportional, with a mean terminal half-life of 3 to 5 days. Conclusions While modest single-agent activity was observed in heavily pretreated NHL patients, the applicability of SGN-CD70A is limited by the frequency and severity of thrombocytopenia, despite the long-term response with limited drug exposure. Electronic supplementary material The online version of this article (10.1007/s10637-018-0655-0) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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