On October 26, 2022 Oncopeptides AB (publ) (NASDAQ Stockholm: ONCO), a biotech company focused on research and development of therapies for difficult-to-treat hematological diseases, reported that data from the phase 3 LIGHTHOUSE study that further confirms the clinical benefit of melflufen in patients with relapsed refractory multiple myeloma (RRMM) (Press release, Oncopeptides, OCT 26, 2022, View Source [SID1234622411]). The LIGHTHOUSE study investigated the efficacy and safety of the combination of melflufen plus daratumumab subcutaneous (sc) plus dexamethasone in comparison with daratumumab sc. (with supportive dexamethasone) in patients who were refractory to at least an immunomodulatory agent and a proteasome inhibitor or have received at least three prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent.
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LIGHTHOUSE is a randomized, open label phase 3 trial, designed as a confirmatory study in addition to the phase 3 OCEAN study. The primary endpoint was progression free survival (PFS). The study started in December 2020 and was planned to include 240 patients. In July 2021, the US Food and Drug Administration (FDA) requested a partial clinical hold of all studies with melflufen. Consequently, patient recruitment in LIGHTHOUSE was halted after 54 patients had been randomized. The clinical study was prematurely terminated in February 2022. Twenty-seven patients were randomized to each treatment arm. Patient characteristics were balanced between the two study arms. The observed efficacy and safety profile for the daratumumab sc. control arm in LIGHTHOUSE was in line with the approval labels in EU and USA with numerically higher PFS and Overall Response Rate (ORR).
Despite the small number of patients enrolled in LIGHTHOUSE at the time of study termination (n=54), the PFS in the ITT population was superior for the melflufen treatment arm in comparison with the control arm with a hazard-ratio (HR) of 0.18 and a nominal p-value of 0.0032. The ITT ORR was superior with a nominal p-value of 0.030, and the ITT Overall Survival (OS) HR was 0.47 with a nominal p-value of 0.37.
"Data from the phase 3 LIGHTHOUSE study are very encouraging and clearly indicate that the combination of melflufen and daratumumab has a clinical benefit in patients with RRMM," says María-Victoria Mateos, MD, PhD, from Salamanca’s University Hospital Haematology Department, and Lead Investigator of the LIGHTHOUSE study. "Multiple myeloma is still an incurable disease for most patients, and we welcome additional evidence on how to combine treatment options with different mode of actions in clinical practice."
In the patient population where the European Medicines Agency (EMA) confirmed melflufen clinical benefit based on the OCEAN trial, the LIGHTHOUSE study (n=29) demonstrated superior PFS with a HR of 0.062 with a nominal p-value of 0.0005, superior ORR with a nominal p-value of 0.0051, and superior OS with a HR of 0.00 with a nominal p-value of 0.037. This patient population excludes patients with post-ASCT time-to-progression <36 months.
"LIGHTHOUSE is the second phase 3 study to confirm the clinical benefit of melflufen in multiple myeloma patients with a treatment history with no stem-cell transplant or a successful prior stem-cell transplant in line with the recent full European approval," said Jakob Lindberg, CEO, Oncopeptides. "In addition, the LIGHTHOUSE data support the EMA conclusion that there is no indication of absolute overall survival harm from treatment with melflufen."
The safety profile of the melflufen and daratumumab sc combination was in line with what was observed in the phase 1/2 ANCHOR study, with predominantly clinically manageable cytopenias. The ANCHOR study was evaluating safety and efficacy of melflufen plus dexamethasone in combination with either daratumumab sc or bortezomib in patients with RRMM.
The information in the press release is information that Oncopeptides is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person above, on October 26, 2022, at 08:00 (CET).