Preliminary trial results show that pre-treatment with the antibody lilotomab may increase the amount of Nordic Nanovector‘s investigational therapy Betalutin that reaches tumor lesions in patients with non-Hodgkin’s lymphoma (NHL).
Representatives from Nordic Nanovector presented their findings at the European Association of Nuclear Medicine annual meeting held Oct. 21-25 in Vienna, Austria.
The oral presentation was titled, “Pre-dosing with Lilotomab Prior to Antibody-Radionuclide Conjugate Therapy with 177Lu-Lilotomab Satetraxetan Significantly Increases the Ratio of Tumour to Red Marrow Absorbed Dose in non-Hodgkin Lymphoma Patients.”
Betalutin is a novel CD37-binding antibody that is labeled with a type of radiation — the beta-emitter lutetium-177 (177Lu). CD37 is highly elevated on most B-cell malignancies, including NHL, 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 facilitates a localized killing of the tumor mass, including cells with or without the CD37 protein. This approach has some advantages over other targeted therapies.
In a Phase 1 trial called LYMRIT-37-01 (NCT01796171), researchers evaluated the uptake of increasing amounts of Betalutin in tumor lesions with or without pre-treatment with lilotomab, the antibody that targets CD37.
Because the protein CD37 is also found in healthy immune cells, Betalutin is linked with hematological toxicity. Lilotomab pre-dosing was expected to lessen this toxicity by reducing the amount of Betalutin that binds to healthy bone marrow cells.
The study included 14 patients with a total of 35 tumor lesions. Using single-photon emission computed tomography (SPECT/CT), a 3D imaging technique that detects gamma radiation in the body, researchers measured the amount of Betalutin in the bone marrow and tumors.
In patients pre-treated with lilotumab, the amount of Betalutin in the bone marrow was significantly lower (35% to 40%) compared to patients who did not receive the pre-treatment. Also, tumor doses were significantly higher among those who received pre-treatment.
“Pre-dosing with lilotomab has a mitigating effect on red marrow absorbed dose for 177Lu-lilotomab satetraxetan patients, and increased pre-dosing amounts was found correlated with a higher tumor dose,” the researchers wrote.
“While the optimal amount of lilotomab is yet to be investigated, both pre-dosage levels significantly increased the tumor to RM [red marrow] absorbed dose ratio.”
Nordic Nanovector’s main investigational therapy in clinical trials is the antibody-radionuclide conjugate Betalutin. This therapy is currently being evaluated in several clinical trials, alone or in combination with other therapies, for the treatment of non-Hodgkin’s lymphoma and relapsed, refractory follicular lymphoma.