By Tristan Manalac  www.biospace.com

Pictured: FDA Building/courtesy of Grandbrothers/Adobe Stock

The FDA has placed Mersana Therapeutics’ UP-NEXT and UPGRADE-A trials on partial clinical hold, the company announced Thursday. Both studies evaluate Mersana’s investigational antibody-drug conjugate upifitamab rilsodotin in platinum-sensitive ovarian cancer.
The regulatory pause was triggered by an aggregate safety report containing information from around 560 patients who had received upifitamab rilsodotin (UpRi). Mersana’s data showed a higher rate of serious bleeding events, though most of these episodes were low-grade.
Still, five cases of serious bleeding were fatal. The exact causes of bleeding are still unknown and are currently being investigated.
Mersana’s stocks fell 60% in pre-market trading Thursday in response to the news.
The FDA has yet to provide Mersana with a formal written communication regarding the partial clinical hold. However, the company expects the regulator to request a more comprehensive evaluation of UpRi’s safety data.
Mersana is working to “compile further analyses that may inform FDA,” Mersana CEO Anna Protopapas said in a statement.
UpRi is a first-in-class antibody-drug conjugate (ADC) that selectively targets the NaPi2b transport protein, an antigen broadly expressed in ovarian cancer, to deliver the company’s proprietary DolaLock payload which is an anti-tubulin auristatin cytotoxic drug.
Mersana is running three studies of UpRi: the Phase III UP-NEXT and Phase I UPGRADE-A in platinum-sensitive ovarian cancer and the Phase I/II UPLIFT in platinum-resistant ovarian cancer.
Thursday’s partial clinical hold disallows the Massachusetts biopharma from recruiting more patients into UP-NEXT and UPGRADE-A, though those already enrolled can continue treatment. Enrollment for UPLIFT was completed in October 2022, and the company expects topline data to start rolling in by August 2023.
UpRi is Mersana’s second molecule to be hit with a clinical hold from the FDA this year. In March, the company’s investigational STING agonist ADC XMT-2056 was also paused after Mersana detected a grade 5 serious adverse event leading to a patient’s death.
The company voluntarily suspended XMT-2056’s Phase I trial after detecting the fatality and is currently investigating the serious adverse event and its potential causes.
In August 2022, GSK inked a global collaboration agreement with Mersana, paying $100 million upfront for the exclusive option to co-develop and commercialize XMT-2056. If GSK exercises its option, and once the clinical hold is lifted, Mersana will also be eligible for up to $1.36 billion in an option exercise payment and development, regulatory and commercial milestones.