Johnson & Johnson's Janssen Biotech will not proceed with stage 2 of the Phase II CARINA LYM2001 trial assessing the marketed cancer drug Darzalex® (daratumumab) in three types of relapsed or refractory non-Hodgkin’s lymphoma (NHL), J&J’s collaboration partner Genmab disclosed.

J&J ended CARINA LYM2001 after Darzalex missed its primary endpoints of overall response rate (ORR) in the trial’s first stage. Two cohorts—relapsed or refractory patients with follicular lymphoma, and with diffuse large B-cell lymphoma—did not reach predefined ORR of 50% and 30%, respectively, according to Genmab.

“While we hoped that daratumumab 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,” Genmab CEO Jan van de Winkel, Ph.D., said yesterday in a statement.

ORR was not evaluable in the study’s third cohort, consisting of patients with mantle cell lymphoma, due to slow recruitment because of the aggressive nature of the disease in its final stages, Genmab added.

CARINA LYM2001 (NCT02413489) is a three-arm, open-label, multicenter study that planned to enroll up to 210 patients in two stages with relapsed or refractory NHL. Stage 1 of the study was designed to provide a preliminary assessment of monotherapy activity, with stage 2 designed to further evaluate safety and efficacy of daratumumab monotherapy. The primary endpoint of the study was ORR.

Genmab said the end of CARINA LYM2001 will not affect other ongoing or planned studies with Darzalex. The drug continues to be studied for indications that include multiple myeloma and other hematological cancers, such as NK/T-cell lymphoma and myelodysplastic syndrome, as well as in solid tumors.

Billion-Dollar Forecasts

While Jefferies analyst Peter Welford last year projected Darzalex could generate $7 billion in peak-year sales, Dr. van de Winkel offered a much rosier forecast to Reuters last month: “It could work in other blood cancers as well as in solid tumors. So that means $13 billion potential if it would work in all the indications.”

Also last month, Dr. van de Winkel told analysts that Genmab estimated 2017 sales for Darzalex of between $1.1 billion and 1.3 billion. The drug generated $572 million in 2016 sales, according to J&J.

Darzalex is a human IgG1k mAb that binds to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. The drug is designed to trigger a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death via apoptosis.

In the U.S., Darzalex is approved as a multiple myeloma treatment for patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent. Darzalex is also approved as part of a combination treatment with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for multiple myeloma patients who have received at least one prior therapy.

In Europe, Darzalex won approval last year as a monotherapy for adults with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy.

Previous articleEA Pharma Licenses MMP-9 mAb from Merck Serono Spin-Out, Calypso
Next articleWith Up-to-$6.8M Grant, Spero Therapeutics to Advance Lead Candidate