Stage 1 of the Phase 2 trial of Darzalex (daratumumab) in relapsed or refractory non-Hodgkin’s lymphomas has failed to reach the predefined thresholds of overall response rates in the follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) groups.
Overall response rate (ORR) for the third cohort was not available. It included mantle cell lymphoma (MCL) patients, who have an aggressive disease in final stages, which slowed patient recruitment.
Based on the findings, Janssen Biotech has decided against proceeding to the second stage of the trial.
The decision will have no impact on other ongoing or planned studies evaluating Genmab’s Darzalex, which is already FDA-approved for relapsed or refractory multiple myeloma.
“While we hoped that daratumumab [Darzalex] as a monotherapy could potentially provide a new treatment option in NHL patients with a high unmet medical need, the preliminary activity profile seen was not sufficient for the study to continue,” Jan van de Winkel, PhD, CEO of Genmab, said in a news release.
“[Darzalex] is still being investigated in a number of indications, including multiple myeloma and other hematological cancers such as NK/T-cell lymphoma and myelodysplastic syndrome as well as in solid tumors,” van de Winkel said.
The open-label, multicenter LYM2001 Phase 2 study (NCT02413489) was designed to evaluate the safety and effectiveness of Darzalex in up to 210 relapsed or refractory non-Hodgkin’s lymphoma patients.
Patients were included in one of three cohorts, DLBCL, FL, or MCL, and received an injection of Darzalex once a week for eight weeks, then once every two weeks for 16 weeks, followed by once every four weeks until disease progression, unacceptable toxicity, or the end of the study.
The study had 2 stages. Stage 1 was designed to provide a preliminary assessment of Darzalex monotherapy, and stage 2 was to further evaluate the drug’s safety and effectiveness.
But data review from stage 1 revealed that the diffuse large B-cell lymphoma and follicular lymphoma cohorts did not reach the 50% and 30% predefined futility thresholds of ORR, respectively. In addition, due to slow recruitment, ORR data on the MCL cohort was not available.
Darzalex is a human antibody that targets the CD38 molecule, which is highly expressed on the surface of myeloma cells and some lymphoma cells. It not only induces direct cancer cell death, but also launches a selective immune attack on cancer cells.