Phase I study of lorvotuzumab mertansine (LM, IMGN901) in combination with lenalidomide (Len) and dexamethasone (Dex) in patients with CD56-positive relapsed or relapsed/refractory multiple myeloma (MM).

Abstract

8013 Background: LM is a conjugate of a maytansinoid cytotoxic agent with a CD56-binding antibody. It is designed to bind to and kill CD56-expressing cancer cells. About 70% of MM cases express CD56. LM has been shown to be active and well tolerated as a single agent for MM in a separate phase I study. Based on the single agent activity and on data from preclinical models of MM showing enhanced activity when LM is combined with Len/Dex, a phase I study assessing the combination was initiated. Methods: The study objectives are to determine the MTD, DLT and activity of LM in combination with fixed doses of Len and Dex. Patients with CD56+ relapsed or relapsed/refractory MM who have received at least 1 prior therapy (may have included Len) are eligible during dose escalation. The total trial is expected to include ~52 patients. Response is assessed per IMWG criteria. LM is given IV once weekly for 3 weeks, Len (25 mg) is given orally on Days 1-21, and Dex (40mg) is given orally once weekly for 4 weeks, all in a 4-week cycle. PK at the MTD is planned, and pharmacodynamic studies are being conducted. Results: Twelve patients have been enrolled (3 patients at 75, 4 at 90, and 5 at 112 mg/m2 of LM). Patient accrual to the 112 mg/m2 cohort continues. No DLTs have been reported. One SAE (fatigue considered related to Dex) and 7 combination-treatment-related grade 3 toxicities have been reported in 4 patients. No grade 4 toxicities have been observed. To date, 2 VGPRs (1 active Cycle 9; 1 off after 6 cycles to receive transplant and 4 PRs (3 active Cycles 2, 3 and 4; 1 off after 4 cycles per patient decision) have been observed; 5 of the 6 responding patients had previously received thalidomide or Len. Among the 12 patients enrolled, the median number of prior therapies is 3, with 42% having received prior Len. Both patients with VGPRs and 1 patient with a PR had prior transplant. Efficacy and safety data for all patients will be reported. Conclusions: LM in combination with Len and Dex has shown objective evidence of clinical activity with an acceptable safety profile. The dose-escalation portion of the study is open to enrollment for further exploration of the MTD.