XMT-1536 on FDA Fast Track for Platinum-resistant, Advanced Ovarian Cancer

XMT-1536 on FDA Fast Track for Platinum-resistant, Advanced Ovarian Cancer

The U.S. Food and Drug Administration (FDA) has given  fast track designation to Mersana TherapeuticsXMT-1536 as a possible treatment for women with platinum-resistant high-grade serous ovarian cancer who received up to three prior lines of therapy.

The designation also covers those who were treated with four different systemic therapies, regardless of their platinum-disease status.

Fast track is meant to facilitate the development and accelerate the review of new medications that aim to treat serious conditions and fill an unmet medical need. Medications given this designation are also eligible for a series of benefits, including the potential for accelerated approval and priority review.

“We are very encouraged by the FDA’s decision to grant us Fast Track Designation for our lead program XMT-1536, which has shown very encouraging activity and tolerability in our Phase 1 study in ovarian cancer to date. We believe this recognition underscores the high unmet medical need for a treatment for patients with platinum-resistant ovarian cancer,” Anna Protopapas, president and CEO of Mersana Therapeutics, said in a press release.

“With this designation in hand, we plan to be able to quickly advance through … XMT-1536’s development and bring forth a therapy for these patients as soon as possible,” Protopapas said.

XMT-1536 is a first-in-class antibody-drug conjugate based on Mersana’s proprietary Dolaflexin platform. The compound is made up of an antibody that recognizes sodium-dependent phosphate transport protein 2b (NaPi2b), a protein found on ovarian and other cancer cells, that is bound to a toxic compound through a biodegradable polymer, called Fleximer.

The polymer — a large molecule made of repeated subunits — is specifically designed to increase XMT-1536’s payload and its effectiveness at destroying cancer cells.

The company launched a Phase 1 trial (NCT03319628) to assess the safety and preliminary efficacy of XMT-1536 in adults with ovarian cancer and non-small cell lung cancer (NSCLC), both likely to contain NaPi2b. Patient recruitment is still underway at several sites across the U.S. More information is available here.

The study includes an initial dose-escalation phase to determine the maximum tolerated or optimal recommended dose of XMT-1536. This is being followed by an expansion phase, where the therapy will be given to two groups of patients (those with ovarian cancer and those with NSCLC) at established doses.

Data from its first part showed at doses of 30 mg/m2 or higher, given once a month, XMT-1536 shrank tumors in 33% of the 15 patients whose tumors contained high levels of NaPi2b, and prevented disease worsening in 40% of the cases.

None of the nine patients given XMT-1536 at similar doses but whose tumors contained low levels of NaPi2b achieved a partial response. Still, the treatment was reported to prevent disease progression in more than half (55%) of the patients.

XMT-1536 was also found to have a favorable safety profile, with the most common treatment-related adverse events reported being only mild to moderate in severity.

Mersana announced that its 43 mg/mdose was well tolerated, and a 52 mg/mdose regimen was beginning to be tested in a January press release.

Data from the second part of the study, which aims to enroll about 45 patients in each cancer group, is expected later this year. Those newly enrolled in this phase of the study will be given XMT-1536 at a dose of 43 mg/m2.