Phase 1 first-in-human study of MEDI2228, a BCMA-targeted ADC, in patients with relapsed refractory multiple myeloma
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 (<i>n</i> = 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 (<i>n</i>=25), ORR was 32%. Although MEDI2228 demonstrated efficacy in R/R MM, ocular toxicity precluded further development of this drug.
Authors
- Shreerang Sirdesai
- Jeremy T. Larsen (ORCID: https://orcid.org/0000-0002-0641-6168)
- Robert Kubiak (ORCID: https://orcid.org/0000-0003-2953-1131)
- Ioannis Kagiampakis
- Miranda Brown
- Shaji Kunnathu Kumar (ORCID: https://orcid.org/0000-0001-5392-9284)
- Nabendu Pore (ORCID: https://orcid.org/0000-0001-6897-0626)
- Farzana L. Walcott (ORCID: https://orcid.org/0000-0003-0779-6972)
- Meletios Α. Dimopoulos (ORCID: https://orcid.org/0000-0001-8990-3254)
- Jeffrey A. Zonder (ORCID: https://orcid.org/0000-0002-1741-2795)
- Sikander Ailawadhi (ORCID: https://orcid.org/0000-0002-8377-8111)
- Manisha Bhutani (ORCID: https://orcid.org/0000-0002-9019-7438)
- Andrew Jenho Yee (ORCID: https://orcid.org/0000-0003-3623-7491)
- Krista Kinneer (ORCID: https://orcid.org/0000-0002-5148-4848)
- Lily Cheng (ORCID: https://orcid.org/0000-0002-3056-1891)
- Magdalini Migkou
- Anna Kalff (ORCID: https://orcid.org/0000-0003-2468-450X)
- Yu Jiang (ORCID: https://orcid.org/0000-0003-4019-8501)
- Yuling Wu (ORCID: https://orcid.org/0000-0002-6922-7452)
- Marna Williams
- Fujun Wang
Institutions
- National and Kapodistrian University of Athens (GR)
- The Alfred Hospital (AU)
- WinnMed (US)
- Massachusetts General Hospital (US)
- The Barbara Ann Karmanos Cancer Institute (US)
- Levine Cancer Institute (US)
- Mayo Clinic in Arizona (US)
- Mayo Clinic in Florida (US)
- AstraZeneca (United States) (US)
Publication Details
- Journal
- Leukemia & lymphoma/Leukemia and lymphoma
- Published
- 2024-10-14
- DOI
- https://doi.org/10.1080/10428194.2024.2373331
- Citations
- 5
- Primary Topic
- Multiple Myeloma Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 2.27