MacroGenics announced that the US FDA has placed a partial clinical hold on the Phase II LINNET study evaluating lorigerlimab, an investigational PD-1×CTLA-4 bispecific DART molecule, in patients with gynecologic cancers.
Under the partial hold, no new patients will be enrolled in the study until the restriction is lifted, although participants currently receiving treatment may continue dosing.
The enrollment pause follows recent safety events reported across four patients in the trial, including Grade 4 thrombocytopenia (n=2), Grade 4 myocarditis (n=1), and Grade 4 neutropenia with concurrent septic shock (n=1), which progressed to a Grade 5 fatal event. To date, 41 patients have been dosed with lorigerlimab at 6 mg/kg every three weeks across platinum-resistant ovarian cancer (PROC) and clear cell gynecologic cancer (CCGC) cohorts.
The Simon two-stage monotherapy study (referring to a trial design enabling evaluation of a single drug in a relatively small group of patients) is designed to enroll patients with PROC who have received up to three prior lines of therapy, with expansion contingent on achieving a predefined activity threshold in an initial cohort of approximately 20 participants. The trial also includes a separate CCGC cohort previously treated with at least one prior line of therapy, with objective response rate serving as the primary endpoint.
MacroGenics said it is working with regulators to address the safety findings and intends to resume enrollment pending resolution of the partial clinical hold.