Safety and efficacy of daratumumab in Chinese patients with relapsed or refractory multiple myeloma: a phase 1, dose-escalation study (MMY1003)

Abstract

Daratumumab monotherapy demonstrated favorable safety and efficacy in relapsed/refractory multiple myeloma (RRMM) patients in the global phase 1/2 GEN501 and phase 2 SIRIUS studies. MMY1003 evaluated daratumumab monotherapy specifically in Chinese patients with RRMM. This 3-part, open-label, phase 1, dose-escalation study included patients with ≥ 2 prior lines of therapy. Part 3 included patients who had received a proteasome inhibitor (PI) and immunomodulatory drug (IMiD) and experienced disease progression on their last regimen. Patients received intravenous daratumumab 8 mg/kg or 16 mg/kg in part 1 and 16 mg/kg in parts 2 + 3. Primary endpoints were dose-limiting toxicity (DLT; part 1), pharmacokinetics (parts 1 + 2), and adverse events (AEs). Fifty patients enrolled. The first 3 patients in part 1 received daratumumab 8 mg/kg; remaining patients in parts 1-3 received daratumumab 16 mg/kg. In the daratumumab 16 mg/kg group (n = 47), patients received a median of 4 prior lines of therapy; 32% were refractory to a PI and IMiD, and 79% were refractory to their last prior therapy. No DLTs occurred. Thirty-six (77%) patients reported grade 3/4 treatment-emergent AEs. Thirteen (28%) patients experienced infusion-related reactions. At an 18.5-month median follow-up, overall response rate was 43%. Median progression-free survival (PFS) and overall survival (OS) were 6.7 months and not reached, respectively; 12-month PFS and OS rates were 35% and 70%. Pharmacokinetic results (n = 22) were consistent with other studies. Safety, pharmacokinetics, and efficacy of daratumumab monotherapy were confirmed in Chinese patients with RRMM. This trial is registered on ClinicalTrials.gov (NCT02852837).

Keywords: CD38; Hematologic malignancies; Monoclonal antibody; Monotherapy; Plasma cell disorders.

Conflict of interest statement

Hongmei Jing, Li Yang, Junyuan Qi, Lugui Qiu, Chengcheng Fu, Junmin Li, Min Yang, and Jie Jin have no conflicts of interest to disclose. Ming Qi is an employee of Janssen and owns stock in Johnson & Johnson. Ni Fan, Jia Ji, and Jiajia Lu are employees of Janssen. Yunan Li is a former employee of Janssen.

© 2022. The Author(s).

Figures

Fig. 1

Mean (± SD) daratumumab serum concentration–time following the first infusion (A) and following the seventh planned infusion (B) in parts 1 and 2 of MMY1003. Post indicates sample taken immediately after infusion; 24 h indicates sample taken 24 h after infusion; pre indicates sample taken before infusion. SD, standard deviation; C, cycle; D, day; h, hour

Fig. 2

Swim-lane plot of patients who achieved ≥ PR in parts 1a, 2b, and 3c in MMY1003. Patient disposition by hematologic response is shown for patients in part 1 plus part 2 who received daratumumab 8 mg/kg (red bars), patients in part 1 plus part 2 who received daratumumab 16 mg/kg (blue bars), and patients in part 3 who received daratumumab 16 mg/kg (gray bars). X indicates disease progression. The asterisk indicates patients whose prior therapy included both a proteasome inhibitor and an immunomodulatory drug and who had demonstrated disease progression on their last therapy. VGPR, very good partial response; sCR, stringent complete response; PR, partial response; CR, complete response. aPatients who achieved ≥ PR in parts 1 + 2 (8 mg/kg dose group): n = 3 out of 3 total patients. bPatients who achieved ≥ PR in parts 1 + 2 (16 mg/kg dose group): n = 9 out of 19 total patients. cPatients who achieved ≥ PR in part 3 (16 mg/kg dose group): n = 11 out of 28 total patients