A Phase 1b trial evaluating a combination of Betalutin (177Lu-satetraxetan-lilotomab) and Rituxan (rituximab) as a second-line therapy for follicular lymphoma will begin soon in Norway following Nordic Nanovector receiving all necessary approvals.
The trial, called Archer-1, is now all set to begin activities immediately. Archer-1 will test the safety and preliminary signs of effectiveness of the combination in roughly 20 patients who have received one prior therapy.
According to a press release, the study will begin conducted in Norway, but additional countries are expected to be added later. The first patient should be dosed in 2018.
Betalutin is an antibody-radionuclide conjugate engineered to work as a form of radiotherapy, in which a radionuclide molecule (a compound that emits radiation to eliminate cancer cells) is linked to an antibody. Because antibodies bind to a specific target only, this combined mechanism of action allows for the delivery of toxic radioactive molecules directly to cancer cells only, killing them while sparing healthy cells.
Specifically, Betalutin’s antibody component binds to the CD37 protein, which is highly expressed on the surface of non-Hodgkin’s lymphoma (NHL) cancer cells.
Currently, most targeted treatments for lymphoma bind to the CD20 molecule, meaning that Betalutin could present an alternative for patients who are non-responsive to CD20-based therapies.
Initial results from an open-label Phase 1/2 study (NCT01796171) suggest that Betalutin reduce tumor size in 90 percent of trial participants who had advanced indolent NHL, including follicular lymphoma patients who had undergone three prior lines of treatment.
Sixty percent of all patients experienced a reduction in their tumors, with 24 percent having achieved a complete response to the therapy. In this trial, Betalutin also was found to be well-tolerated and safe, with patients experiencing only controllable side effects.
These results were presented at the International Conference on Malignant Lymphoma in Switzerland in 2017 and the trial is scheduled to be completed in 2021. Participants in Europe and the U.K. are still being recruited.
Another Phase 1 clinical trial (NCT02657447) also is recruiting participants in Germany to assess the behavior of Betalutin radio-immunotherapy in patients with relapsed NHL. Participants will receive a pre-dosing of lilotomab (a CD37 antibody) to reduce Betalutin’s toxicity to healthy immune cells.
In April, Nordic also announced that a Phase 2b trial evaluating Betalutin as a third-line therapy for follicular lymphoma was moving ahead and expected to open U.S. sites soon.
The study, called PARADIGME, is expected to open in mid-2018, following the U.S. Food and Drug Administration (FDA) approval. The trial will assess two doses of Betalutin in relapsed or refractory follicular lymphoma when patients already have received two previous lines of therapy.
Patients will also be given Betalutin in combination with lilotomab. The trial plans to enroll 130 patients and expand to 20 countries.