Y-mAbs Begins Phase 1 Trial of CD38-SADA Radioimmunotherapy for Relapsed Non-Hodgkin Lymphoma

NEW YORK, NY, USA I April 25, 2025 I Y-mAbs Therapeutics, Inc. (Nasdaq: YMAB), a company at the forefront of biopharmaceutical innovations, has announced a significant milestone in its pursuit of enhanced cancer treatments. The company has successfully administered the first doses to a patient in its groundbreaking Phase 1 clinical trial, which explores its Self-Assembly and Disassembly (SADA) Pre-targeted Radioimmunotherapy (PRIT) platform. This trial specifically targets individuals suffering from relapsed or refractory non-Hodgkin Lymphoma (r/r NHL). Trial 1201 serves as a key investigation into the safety and tolerability of the CD38-SADA: ^177Lu-DOTA Drug Complex.

The structure of Trial 1201 is a dose-escalation, open-label, single-arm, multi-center design. At its core, the study focuses on the innovative pre-targeted delivery method of the CD38-SADA protein, which shows a strong affinity for binding to lymphoma cells. Following this protein administration, a radioactive payload (^177Lu-DOTA) is introduced, which is specifically targeted at the CD38-SADA molecules attached to the tumor cells. This method aims to maximize tumor targeting while minimizing radiation exposure to healthy tissues. Part A of the trial is dedicated to escalating the CD38-SADA dose, with a consistent ^177Lu-DOTA dose, to determine the optimal protein dose and timing between the protein and payload administrations. Primary goals for this phase include tumor imaging and monitoring for any dose-limiting toxicities.

Dr. Norman LaFrance, the Chief Development and Medical Officer at Y-mAbs, expressed enthusiasm about this development. "We're thrilled to have dosed the first patient in Trial 1201, marking our second clinical program utilizing the SADA PRIT platform and our first venture into hematological malignancies," he stated. Dr. LaFrance highlighted the significant challenges faced by patients with relapsed or refractory NHL, who often contend with limited treatment choices and a more severe disease progression. He believes that Y-mAbs' pre-targeted radioimmunotherapy approach could offer improved outcomes for this vulnerable patient group.

Beyond the current trial, the SADA PRIT platform's modularity has paved the way for developing other bispecific fusion proteins, such as GD2-SADA, which is being evaluated for treating tumors expressing GD2. The SADA technology, central to Y-mAbs' innovations, was developed by researchers at Memorial Sloan Kettering Cancer Center (MSK), including Dr. Nai-Kong Cheung. MSK holds exclusive licensing rights to this technology, with Dr. Cheung having intellectual property interests and rights. Consequently, MSK also has financial interests in this technological advancement.

Y-mAbs Therapeutics, Inc. is a biopharmaceutical company in the commercialization stage, dedicated to developing novel radioimmunotherapy and antibody-based products for cancer treatment. The company's technology portfolio includes the investigational SADA PRIT platform and bispecific antibodies produced through the Y-BiClone platform. Among its notable achievements is the development of DANYELZA® (naxitamab-gqgk), an anti-GD2 therapy that received FDA approval for treating patients with relapsed or refractory high-risk neuroblastoma in bone or bone marrow after limited responses to prior treatment.

The CD38-SADA PRIT employs a bispecific fusion protein that effectively binds to the CD38 glycoprotein and ^177Lu-tetraxetan (^177Lu-DOTA), a radionuclide. In the pre-targeted radioimmunotherapy process's initial phase, CD38-SADA tetramers are administered to bind with CD38-expressing lymphoma cells. Any unbound CD38-SADA disassembles into smaller monomers and is excreted by the kidneys. The subsequent step involves delivering the radioactive payload, which attaches directly to the tumor-bound CD38-SADA, facilitating precise tumor irradiation. This method has shown promising anti-tumor efficacy in preclinical studies and is currently being explored in adults with relapsed, progressive, or refractory NHL after undergoing at least two previous therapies.