NEW YORK – Y-mAbs Therapeutics began a Phase I clinical trial of its GD2-SADA antibody construct with 177Lu-DOTA in patients with GD2-positive malignant melanoma, sarcoma, and small cell lung cancer.
The trial is a step forward for the New York-based company after it announced in January that it is restructuring its operations and deprioritizing its Omblastys (omburtamab) program. Y-mAbs said in December that the US Food and Drug Administration issued a complete response letter for Y-mAbs' biologic license application for the B7-H3-targeted radiotherapy as a treatment for CNS or leptomeningeal metastasis from neuroblastoma, stating that it is unable to approve the application in its current form. That was followed by the European Medicines Agency's Committee for Medicinal Products for Human Use recommending against marketing authorization in Europe.
Y-mAbs, now focused on advancing its radioimmunotherapy, will conduct the recently launched Phase I trial in three parts, aiming to enroll around 60 patients. In the part A dose-escalation phase, investigators will test a range of dosing intervals between GD2-SADA and the 177Lu-DOTA payload in a single dosing cycle. Y-mAbs will determine an optimal dose in up to two treatment cycles in part B of the trial, and in part C, the firm will assess safety and look for initial signs of efficacy for up to five treatment cycles. It will also collect imaging data to assess tumor targeting and assess the pharmacokinetic profile of the therapy.
GD2-SADA was developed on Y-mAbs' two-step Self-Assembly and DisAssembly-Bispecific DOTA-Engaging antibody system (SADA-BiDE) pre-targeted radioimmunotherapy platform at Memorial Sloan Kettering Cancer Center and licensed exclusively to Y-mAbs. The therapy comprises a set of antibody constructs that assemble in tetramers and bind to the tumor target to deliver a payload — in this case 177Lu-DOTA — which is delivered in a second infusion.