CD56-Targeting ADC Found Safe and Active in Relapsed or Refractory Multiple Myeloma
Results from a phase 1 trial for the investigational ADC in multiple myeloma led investigators to conclude it may be viable in combination.
A phase I study of the CD56-targeting lorvotuzumab mertansine showed the drug to be safe and active in patients with relapsed or refractory multiple myeloma.1
Lorvotuzumab mertansine is an antibody-drug conjugate targeting CD56, which is frequently expressed on multiple myeloma cells. Additionally, CD56 is expressed on less than 15% of normal cells, making it a useful marker of disease and an attractive therapeutic target.
In this phase I study, 37 patients with relapsed myeloma were enrolled in a dose-escalation trial. Three patients each were enrolled at 40, 60, 75, 90, and 112 mg/m2 and 6 patients were enrolled at 140 mg/m2. Two patients experienced dose-limiting toxicities at the highest dose, so 112 mg/m2 was established as the maximum-tolerated dose. An expansion phase included 16 additional patients treated at the 112 mg/m2 dose.
Thirty-five of the 37 patients were included in the efficacy evaluable cohort.
About six in 10 (56.8%) patients had relapsed or refractory myeloma. Despite that, stable disease or better was found in 42.9% of patients, with a median duration of response of 15.5 months. Partial response occurred in 5.7% of patients and 11.4% had minor response. No patient achieved very good partial response or complete response. Median progression-free survival was 26.1 weeks.
Eighty-nine percent of patients experienced an adverse event related to the study. Drug-related peripheral neuropathy occurred in 51% of patients. Grade 3 or 4 drug-related adverse events resulted in drug discontinuation in 9 patients; the most common event was peripheral neuropathy.
According to the researchers, “the safety and efficacy signal” from this ADC warrants its further clinical development — in combination with other agents — for patients with multiple myeloma.
Disclosure: Authors of the original study declare various ties to pharmaceutical companies. For a full list of disclosures, please refer to the original study.
- Ailawadhi S, Kelly KR, Vescio RA, et al. A phase I study to assess the safety and pharmacokinetics of single-agent lorvotuzumab mertansine (IMGN901) in patients with relapsed and/or refractory CD-56-positive multiple myeloma [published online September 5, 2018]. Clin Lymphoma Myeloma Leuk.doi: 10.1016/j.clml.2018-08-018