MM-169: ANCHOR (OP-104): Melflufen Plus Dexamethasone and Bortezomib in Relapsed/Refractory Multiple Myeloma (RRMM)—Optimal Dose, Updated Efficacy and Safety Results

Abstract

Context Development of resistance to standard treatments for RRMM highlights the need for novel therapies. Melphalan flufenamide (melflufen) is a first-in-class peptide–drug conjugate (PDC) that targets aminopeptidases and rapidly releases alkylating agents inside tumor cells. Melflufen plus dexamethasone showed clinical activity and an acceptable safety profile in HORIZON (Richardson et al. J Clin Oncol. 2021;39:757-767). Objective To provide an update of the bortezomib arm from the phase 1 part of the ANCHOR study (NCT03481556). Methods Patients with RRMM were intolerant of or refractory to a prior immunomodulatory agent, with 1-4 prior lines of therapy (LoTs). Prior treatment with a proteasome inhibitor (PI) was allowed, but patients could not be refractory to PIs in the last LoT. Melflufen (30, 40, or 20 mg intravenously; day 1 of each 28-day cycle) was administered with bortezomib (1.3 mg/m2 subcutaneous on days 1, 4, 8, and 11) plus oral dexamethasone (20 mg on days 1, 4, 8, and 11; 40 mg on days 15 and 22; dose reduced if aged ≥75 years). The primary objective was to determine the optimal phase 2 dose of melflufen for this combination. Results As of the data cutoff date (October 19, 2020), 13 patients received melflufen (30 mg, n=6; 40 mg, n=7) plus dexamethasone and bortezomib. In the 30-mg and 40-mg groups, respectively, median age was 78.5 years (range, 70–82) and 70.0 years (range, 61–76); 100% and 86% received a prior PI; 33% and 14% were refractory to PIs. Confirmed overall response rate (defined as ≥ partial response) was 50% and 71%, in each group, respectively. Most common grade 3/4 treatment-related AEs (TRAEs) were thrombocytopenia (30 mg, 50%; 40 mg, 100%) and neutropenia (30 mg, 33%; 40 mg, 71%); 3 patients discontinued study treatment due to treatment-emergent AEs. Serious TRAEs occurred in 3 patients (30 mg, n=2; 40 mg, n=1). No dose-limiting toxicities occurred at either dose level. Fatal AEs occurred in 1 patient in the 30-mg group (unrelated to study treatment). Conclusions ANCHOR determined that the optimal dose of melflufen is 30 mg plus dexamethasone and bortezomib; results showed clinical activity in heavily pretreated patients. Recruitment is ongoing.