Phase 1 first-in-human study of MEDI2228, a BCMA-targeted ADC, in patients with relapsed refractory multiple myeloma.

Autor: Dimopoulos MA; Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece., Migkou M; Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece., Bhutani M; Atrium Health, Levine Cancer Institute, Charlotte, NC, USA., Ailawadhi S; Mayo Clinic, Jacksonville, FL, USA., Kalff A; The Alfred Hospital, Melbourne, Australia., Walcott FL; Early Oncology Research and Development, AstraZeneca, Gaithersburg, MD, USA., Pore N; Early Oncology Research and Development, AstraZeneca, Gaithersburg, MD, USA., Brown M; Early Oncology Research and Development, AstraZeneca, Gaithersburg, MD, USA., Wang F; Early Oncology Research and Development, AstraZeneca, Gaithersburg, MD, USA., Cheng LI; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD, USA., Kagiampakis I; Translational Medicine Bioinformatics, AstraZeneca, Gaithersburg, MD, USA., Williams M; Translational Medicine, AstraZeneca, Gaithersburg, MD, USA., Kinneer K; Translational Medicine, AstraZeneca, Gaithersburg, MD, USA., Wu Y; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD, USA., Jiang Y; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD, USA., Kubiak RJ; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD, USA., Zonder JA; Karmanos Cancer Institute, Detroit, MI, USA., Larsen J; Mayo Clinic, Scottsdale, AZ, USA., Sirdesai S; The Alfred Hospital, Melbourne, Australia., Yee AJ; Massachusetts General Hospital, Boston, MA, USA., Kumar S; Mayo Clinic, Rochester, MN, USA.
Jazyk: angličtina
Zdroj: Leukemia & lymphoma [Leuk Lymphoma] 2024 Dec; Vol. 65 (12), pp. 1789-1800. Date of Electronic Publication: 2024 Oct 15.
DOI: 10.1080/10428194.2024.2373331
Abstrakt: MEDI2228 is an antibody drug conjugate (ADC) comprised of a fully human B-cell maturation antigen (BCMA) antibody conjugated to a pyrrolobenzodiazepine (PBD) dimer. This phase 1 trial evaluated MEDI2228 in patients with relapsed/refractory (R/R) multiple myeloma (MM), who received prior treatment with approved agents from 3 classes of antimyeloma drugs (proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies). Primary endpoint was safety and tolerability; secondary endpoints included efficacy, pharmacokinetics, and immunogenicity. A total of 107 patients were treated and the maximum tolerated dose (MTD) was 0.14 mg/kg Q3W. Two patients had dose-limiting toxicities (DLTs; thrombocytopenia; 0.20 mg/kg Q3W). The most frequent treatment-related adverse events were photophobia (43.9%), rash (29.0%), and thrombocytopenia (19.6%). In MTD cohort A ( n  = 41), the objective response rate (ORR) was 56.1%, with 1 stringent complete response, 9 very good partial responses, and 13 partial responses. ORR was 53.3% in triple refractory patients. In cohort B ( n =25), ORR was 32%. Although MEDI2228 demonstrated efficacy in R/R MM, ocular toxicity precluded further development of this drug.
Databáze: MEDLINE