A Phase 2b trial evaluating Betalutin — a tumor-targeting antibody labeled with a type of radiation — as a third-line therapy for follicular lymphoma patients will conclude a little later than planned, but is moving ahead and expects to open U.S. sites soon.
The announcement, by Nordic Nanovector, followed an assessment of recruitment rates at trial sites already open in Europe, which made it clear the study — called PARADIGME — would not finish in late 2019 as planned, but rather in early 2020. Dosing of a first patient is now likely at mid-year, the company said in a press release.
U.S. sites for PARADIGME are also expected to open in mid-2018 and begin recruiting patients; the U.S. Food and Drug Administration has finished its review of the trial, Nordic added.
“While we are encouraged with the progress being made to the start-up of the pivotal PARADIGME study, a re-analysis of the patient enrolment rate and the fact that it has taken longer than expected to enrol the first patient have led us to adjust the timelines … We now expect to deliver data from PARADIGME in the first half of 2020,” said Lisa Rojkjaer, the company’s chief medical officer.
Betalutin is a CD37-binding antibody that is labeled with a type of radiation: the beta-emitter lutetium-177 (177Lu). CD37 is highly produced on most B-cell malignancies, including non-Hodgkin’s lymphoma, making it a promising therapeutic target.
By linking the CD37 antibody with 177Lu, radiation can be specifically targeted toward the tumor mass. The beta-radiation is reported to facilitate a localized killing of the tumor mass, including cells with or without the CD37 protein.
In an open-label Phase 1/2 trial — called LYMRIT 37-01 (NCT01796171) — researchers tested increasing amounts of Betalutin, with different pre-dosing treatments, in non-Hodgkin’s lymphoma patients whose disease relapsed. The treatment showed promising clinical activity in data presented at a June 2017 scientific conference, with 64% of patients responding, including 28% complete responses.
Data also showed that Betalutin has a significant activity in a subgroup of relapsed follicular lymphoma patients, with 70% of achieving either a partial or a complete response.
PARADIGME will assess two Betalutin dosing regimens in relapsed or refractory follicular lymphoma patients who received two prior lines of therapy. Patients will be given Betalutin in combination with lilotomab (the CD37 antibody in Betalutin), which reduces Betalutin’s toxicity to healthy immune cells.
The trial aims to enroll 130 patients in 20 countries.
“The PARADIGME study reflects our conviction in the significant potential of Betalutin based on the promising clinical data generated to-date,” Rojkjaer said. “We therefore remain committed to completing this robust study, which is designed to select the best dosing regimen to support Betalutin as an important new treatment option for 3L FL patients.”
Two other clinical trials will continue as expected, Nordic said.
ARCHER-1 will begin patient enrollment in the second half of 2018 to evaluate Betalutin in combination with Rituxan (rituximab) in follicular lymphoma patients who received one prior line of therapy.
LYMRIT 37-05 (NCT02658968) is currently assessing Betalutin in patients with relapsed or refractory diffuse large B-cell lymphoma. Preliminary data from this Phase 1 trial is anticipated later this year.
But a planned first-in-human study of Humalutin as a possible non-Hodgkin’s lymphoma treatment is being postponed to focus resources on PARADIGME. That trial was expected to start in late 2018.