XMT-1536 is a first-in-class antibody-drug conjugate (ADC) targeting the sodium-dependent phosphate transport protein (NaPi2b) using the Dolaflexin platform developed by Mersana Therapeutics, a clinical-stage biopharmaceutical company, to deliver an average of 10-15 DolaLock payload molecules per antibody.
Earlier this week, the investigational ADC targeting cancers in areas of high unmet medical need, was used to dose the first patient in the expansion portion of the Phase I study. The expansion cohorts will assess the efficacy, safety and tolerability of XMT-1536 at 36 mg/m2 every four weeks in patients with platinum-resistant ovarian cancer and non-small cell lung cancer (NSCLC) adenocarcinoma.
Mersana also announced that it has not determined a maximum tolerated dose and that it plans to continue the dose escalation portion of the study in parallel.
“The initiation of the expansion cohorts is an important milestone for Mersana. We have chosen a dose that continues to show a promising efficacy and tolerability profile in heavily pretreated patients without selecting for NaPi2b expression,” said Anna Protopapas, President and CEO of Mersana Therapeutics.
“The advancement of XMT-1536 brings us one step closer to proof of concept and our goal of significantly improving outcomes for people living with cancer,” Protopapas observed.
“We are excited to move XMT-1536 into this important next phase of clinical development. With additional sites participating in the expansion cohorts we look forward to establishing the benefits of XMT-1536 in larger, more defined patient populations with high unmet medical need,” noted Dirk Huebner, M.D., Chief Medical Officer of Mersana Therapeutics.
“In addition, because we have not determined a maximum tolerated dose and have not observed the severe toxicities seen with other ADC platforms (e.g., neutropenia, peripheral neuropathy or ocular toxicity), we plan to continue dose escalation and will begin dosing patients at 43 mg/m2. Taken together, the ongoing expansion and dose escalation studies will provide critical information to guide our path to registration for XMT-1536,” he added.
The expansion study includes two patient cohorts. One is enrolling platinum-resistant ovarian cancer patients who have failed standard therapy and have had no more than three lines of prior therapy. The other cohort is enrolling NSCLC adenocarcinoma patients who have failed front line platinum-based chemotherapy, either in combination or sequentially treated with an anti-PD-1 or anti-PD-L1 therapy. Patients in the expansion portion of the XMT-1536 Phase 1 study will be treated with the 36 mg/m2 once-every-four-week dosing regimen. Patients will not be pre-selected for NaPi2b expression, but eligibility criteria require archived tumor samples and fresh tumor biopsies when medically feasible.
First-in-Human Study of XMT-1536 in Cancers Likely to Express NaPi2b – NCT03319628