After pulling Blenrep from the U.S. market in the fall, GSK's antibody-drug conjugate (ADC) strategy has stumbled again. This time, Mersana Therapeutics' cancer drug has been slapped with a clinical hold after a patient in the therapy’s first trial died. The news comes only six months after GSK paid $100 million for the license option.
Mersana had already informed the FDA that it was voluntarily pausing the study of the asset, dubbed XMT-2056, after a patient suffered a fatal serious adverse event that was deemed to be related to the therapy, the biotech said in a release this morning.
The single-group study was due to recruit over 170 patients with advanced or recurrent solid tumors expressing HER2, according to ClinicalTrials.gov. The patient who died was the second participant to receive the initial dose level in the dose-escalation portion of the study, Mersana said.
Developed using Mersana’s immunosynthen platform, XMT-2056 is designed to activate the innate immune system through STING signaling—a key pathway in tumor control. As the first of the biotech’s STING-agonist ADC candidates to enter the clinic, there was a lot riding on XMT-2056’s smooth progress through the clinic. Last May, the FDA tagged the asset with an orphan-drug designation for gastric cancer.
“In line with our steadfast commitment to patient safety, we have been proactive in our response to this event,” Mersana CEO Anna Protopapas said in the release. “With the clinical hold in place, our efforts for XMT-2056 are now focused on undertaking the work required to fully analyze this SAE and consider potential next steps for development.”
Meanwhile, the company will continue with its UpRi and XMT-1660 clinical trials, which it pointed out are unaffected by the hold on XMT-2056. UpRi, also known as upifitamab rilsodotin, is a dolaflexin ADC in a phase 3 trial for NaPi2b-positive recurrent platinum-sensitive ovarian cancer. XMT-1660 is a B7-H4-directed dolasynthen ADC in a phase 1 trial for breast, endometrial and ovarian cancers.
Despite this reassurance, Mersana’s stock dipped slightly over 12%, opening at $4.06 after closing Friday at $4.62.
The clinical hold is unwelcome news for GSK, which paid $100 million cash last August for the exclusive option to co-develop and commercialize XMT-2056. The Big Pharma has one other ADC in its portfolio in the form of Blenrep, which was approved in 2020 for multiple myeloma patients who have failed four previous treatments.
However, Blenrep was plagued by its own adverse events. Nearly 75% of clinical trial patients suffered eye problems, some so serious that they led to vision loss, prompting regulators to include the dreaded “black box” warning on the drug’s label.
The British Big Pharma would go one step further in November 2022, pulling Blenrep from the U.S. market at the request of the FDA after the ADC failed to top a pairing of Bristol Myers Squibb’s Pomalyst and dexamethasone in relapsed or refractory multiple myeloma after at least two prior lines of therapy.
In a statement responding to the news, GSK emphasized that XMT-2056 remains wholly owned by Mersana, with the British Big Pharma retaining the option to co-develop the therapy further down the line.
“Patient safety is our priority, and our thoughts are with the family and friends of the patient,” GSK added.