A phase 1 trial of SGN-CD70A in patients with CD70-positive diffuse large B cell lymphoma and mantle cell lymphoma. Invest New Drugs 2019 Apr;37(2):297-306
Date
08/23/2018Pubmed ID
30132271Pubmed Central ID
PMC6440937DOI
10.1007/s10637-018-0655-0Scopus ID
2-s2.0-85052586700 (requires institutional sign-in at Scopus site) 65 CitationsAbstract
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.
Author List
Phillips T, Barr PM, Park SI, Kolibaba K, Caimi PF, Chhabra S, Kingsley EC, Boyd T, Chen R, Carret AS, Gartner EM, Li H, Yu C, Smith DCMESH terms used to index this publication - Major topics in bold
AdultAged
Aged, 80 and over
Antibodies, Monoclonal
Benzodiazepines
Biomarkers, Tumor
CD27 Ligand
Drug Resistance, Neoplasm
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Humans
Immunoconjugates
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Mantle-Cell
Male
Maximum Tolerated Dose
Middle Aged
Neoplasm Recurrence, Local
Prognosis
Pyrroles
Salvage Therapy
Tissue Distribution
