MacroGenics Inc (NASDAQ: MGNX) experienced a 7.4% drop in premarket trading Tuesday after the company disclosed that the U.S. Food and Drug Administration has instituted a partial clinical hold on its LINNET study of lorigerlimab in patients with gynecologic cancers.
Under the terms of the partial clinical hold, the trial will not enroll any new patients until the FDA lifts the restriction. MacroGenics confirmed that current study participants are permitted to continue receiving the study drug while the hold is in place.
The FDA action followed MacroGenics notifying regulators of a temporary enrollment pause after a cluster of safety events. Safety issues were reported across four patients in the trial and included two instances of Grade 4 thrombocytopenia, one instance of Grade 4 myocarditis, and one instance of Grade 4 neutropenia that occurred with concurrent septic shock and resulted in a Grade 5 outcome.
To date, the company has dosed 41 participants at 6 mg/kg administered every three weeks across cohorts for platinum-resistant ovarian cancer and for clear cell gynecologic cancer. The study design calls for lorigerlimab as monotherapy in eligible patients with platinum-resistant ovarian cancer who have received up to three prior lines of therapy, and for enrollment of up to 20 patients with clear cell gynecologic cancer who have received at least one prior line of therapy. The primary endpoint of the LINNET study is objective response rate.
In response to the FDA action, MacroGenics President and CEO Eric Risser emphasized patient safety as the company's foremost priority and stated the company will work closely with the agency to resolve the partial clinical hold, with the intention to resume enrollment as soon as possible.
Context and operational details
The partial clinical hold follows MacroGenics' earlier decision to temporarily pause enrollment while safety events were investigated. The company reported that the adverse events occurred across four patients in the study, prompting both the internal pause and the subsequent FDA-imposed restriction on new enrollment.
As reported by MacroGenics, dosing to date consists of 41 patients receiving lorigerlimab at the specified 6 mg/kg every-three-weeks regimen across the platinum-resistant ovarian cancer cohort and the clear cell gynecologic cancer cohort. The LINNET protocol was structured to evaluate objective response rate as the primary measure of efficacy.
MacroGenics has indicated its commitment to resolving the partial clinical hold with regulators and to resuming patient enrollment when cleared to do so.