The regulator has released Mersana Therapeutics’ antibody-drug conjugate XMT-2056 from its clinical hold, allowing the biotech to proceed with Phase I studies of the candidate with a lower starting dose.
Pictured: FDA sign outside its office in Maryland/iStock, hapabapa
The FDA has lifted its full clinical hold on Mersana Therapeutics’ Phase I study of XMT-2056, its investigational STING-directed antibody-drug conjugate, the company announced Tuesday.
The clinical hold came in March 2023, following a patient death that was deemed related to XMT-2056. At the time, Mersana was assessing the candidate in a Phase I trial, enrolling previously treated patients with HER2-positive recurrent or metastatic solid tumors.
The fatality occurred in the second patient enrolled in the dose-escalation phase of the early-stage study, pushing the biotech to voluntarily suspend the trial and report the incident to the regulator.
In Tuesday’s announcement, Mersana indicated that it was lowering the starting dose of XMT-2056 in its study and that it has “aligned with FDA on the path forward” for the investigational therapy.
Mersana rose 7% in late morning trading following the news, according to Seeking Alpha.
Discovered and developed using Mersana’s proprietary Immunosynthen platform, XMT-2056 is an investigational antibody-drug conjugate (ADC) that targets a novel HER2 epitope and activates the STING signaling cascade in tumors and tumor-resident immune cells, according to the company’s website.
This mode of action allows it to boost the anti-tumor action of the innate immune response, and has the potential to treat cancers with high or low HER2 expression levels. In August 2022, GSK bought into the promise of XMT-2056 in a global collaboration deal worth $100 million upfront and the promise of up to $1.36 billion in development, regulatory and commercial milestones.
Under the agreement, GSK will have the exclusive option for global commercialization rights over XMT-2056, while Mersana will retain the option for profit-sharing and co-promotion in the U.S.
On Wednesday, however, GSK announced in a pipeline update that it was dropping an early-stage in-house STING agonist, dubbed 3745417. The British pharma has not yet exercised its option in the Mersana deal, and it remains unclear whether the discontinuation of 3745417 will affect the prospects of XMT-2056.
In January 2023, Mersana kicked off the Phase I trial for XMT-2056, with an estimated enrollment target of around 170 patients with advanced or recurrent HER2-expressing solid tumors, including breast, gastric, non-small cell lung and colorectal cancers.
Mersana has two other trials under regulatory pause. In June 2023, the FDA placed the company’s UP-NEXT and UPGRADE-A studies on partial clinical hold following an aggregate safety report from some 560 patients showing a higher rate of serious bleeding events in patients treated with the investigational ADC upifitamab rilsodotin (UpRi).
Most of the bleeds were low-grade, according to Mersana’s announcement at the time, but five were ultimately fatal. UP-NEXT and UPGRADE-A are assessing UpRi in platinum-sensitive ovarian cancer.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
