MK-4002, a B-cell maturation antigen-targeting T-cell engager, in relapsed or refractory multiple myeloma: a first-in-human, open-label, phase 1 study.
Sumit Madan, Caitlin Costello, Brea Lipe et al.
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In 30 seconds
This first-in-human, open-label, multicentre phase 1 study evaluated the safety, pharmacokinetics, and preliminary activity of the BCMA-targeting T-cell engager MK-4002 in adults with heavily pretreated relapsed or refractory multiple myeloma. Among 97 treated participants, the overall response rate was 63% in the 12 mg group (19 participants); a 12 mg target dose was selected as the preliminary recommended phase 2 dose. Adverse events were common, and cytokine release syndrome occurred in 30%. The study remains ongoing but is closed to recruitment.
Key findings
- Overall response rates were 41% (95% CI 22-61) at 2·15-6 mg, 63% (38-84) at 12 mg, and 48% (31-67) at 24 mg.
- Adverse events occurred in all 97 participants; 77 (79%) had grade 3 or worse events.
- Cytokine release syndrome occurred in 29 participants (30%); 27 cases were grade 1-2 and two were grade 3.
- The fixed-dose maximum tolerated dose was 2·15 mg; 12 mg was identified as the preliminary recommended phase 2 target dose.
Why it matters
The study provides early clinical evidence about a BCMA-directed T-cell engager in a population with substantial prior treatment exposure, while characterising dose-related safety and preliminary response. The response findings and selection of a phase 2 target dose support further evaluation, but the phase 1 design and non-comparative results do not establish benefit relative to other treatments.
What to keep in mind
This was an open-label, non-randomised phase 1 study with dose-escalation cohorts and no comparator; response estimates come from relatively small dose groups.