NEW YORK – Mersana Therapeutics said on Tuesday that the US Food and Drug Administration has lifted the clinical hold on the company's Phase I clinical trial of its HER2-targeting antibody-drug conjugate XMT-2056.
Mersana said it has lowered the starting dose of XMT-2056 in the dose escalation stage of the trial. The trial was put on hold in March after a patient who received the initial dose level in that portion of the study died, a death that was believed to be related to treatment.
"An in-depth analysis of cytokine, pharmacokinetic, and other clinical data from patients enrolled in our Phase I trial indicated that XMT-2056 is a highly potent innate immune agonist," Mersana CEO Martin Huber said in a statement. "Based on these data and with patient safety at the forefront of our efforts, we have lowered the starting dose in our Phase I dose escalation design. We are pleased to have aligned with FDA on the path forward and are excited to have the opportunity to continue to investigate the potential of XMT-2056 and our Immunosynthen ADC platform in the clinic."
The trial is evaluating XMT-2056 in previously treated patients with advanced/recurrent solid tumors expressing HER2, including breast, gastric, colorectal, and non-small-cell lung cancers. The trial will enroll approximately 171 patients across the dose escalation and dose expansion portions.
Mersana, based in Cambridge, Massachusetts, entered into a license option agreement with GlaxoSmithKline for XMT-2056 last year. GSK paid $100 million upfront for the option to exclusively license XMT-2056 for development and commercialization. If GSK exercises the option, Mersana will receive up to $1.36 billion in option exercise and potential milestone payments.
In 2022, the FDA granted orphan drug designation to XMT-2056 for the treatment of patients with gastric cancers. The drug was developed using Mersana's Immunosynthen STING agonist platform, which generates ADCs that locally activate STING signaling in both tumor-resident immune cells and in antigen expressing cells.