BRIDGE (OP-107): A Phase 2 Pharmacokinetic Study of Melflufen Plus Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma and Impaired Renal Function.

BACKGROUND

Information about safety and pharmacokinetics (PK) of melflufen (melphalan flufenamide) is limited in renal impairment (RI) patients. The BRIDGE study evaluated the impact of renal function on PK of the main alkylating agent of melflufen, melphalan, and assessed the safety of melflufen plus dexamethasone in relapsed/refractory multiple myeloma (RRMM) patients.

METHODS

BRIDGE was a Phase 2, open-label study in RRMM patients with moderate (estimated glomerular filtration rate [eGFR] ≥30 to <45 mL/min/1.73 m²) or severe (eGFR ≥15 to <30 mL/min/1.73 m2) RI. Patients received melflufen 20 to 40 mg intravenously every 28 days, plus weekly dexamethasone 40 mg. Three post-infusion blood samples were collected in Cycles 1 and 2. Primary endpoints were safety and melphalan PK.

RESULTS

Thirty-five RRMM patients were enrolled; Cohort 1a (n=21; moderate RI, melflufen 40 mg), Cohort 1b (n=10; moderate RI, melflufen 30 mg), and Cohort 2a (n=4; severe RI, melflufen 20 mg). In Cycle 1, mean Cmax and AUCinf were lower in Cohort 1b (472.2 ng/mL and 1286.2 h·ng/mL, respectively) and Cohort 2a (181.2 ng/mL and 528.5 h·ng/mL, respectively) compared to Cohort 1a (550.2 ng/mL and 1418.7 h·ng/mL, respectively). Mean elimination half-life increased slightly with declining renal function (Cohort 1a to 2a: 89.1-109.6 min). Treatment-emergent adverse events occurred in 34 patients and 6 patients died due to a treatment-emergent adverse events.

CONCLUSIONS

PK results from the BRIDGE study support the recommended dose of melflufen 30 mg for moderate RI patients. No new safety signals were reported in RRMM patients with moderate-to-severe RI.