FDA Places Partial Clinical Hold on MacroGenics' Lorigerlimab Trial Following Severe Safety Events
Key Insights
The FDA has placed a partial clinical hold on MacroGenics' Phase 2 LINNET study of lorigerlimab, a bispecific DART molecule targeting PD-1 (search) and CTLA-4 (search), in gynecologic cancers (search) following severe safety events in four patients.
Safety events included Grade 4 thrombocytopenia (search) in two patients, Grade 4 myocarditis (search) in one patient, and Grade 4 neutropenia (search) with septic shock (search) leading to one death across 41 dosed participants.
Current study participants may continue receiving treatment while no new patients can be enrolled until the FDA lifts the hold, with MacroGenics committed to working with regulators to resolve the safety concerns.
MacroGenics announced that the U.S. Food and Drug Administration has placed a partial clinical hold on its Phase 2 LINNET study of lorigerlimab, an investigational bispecific DART molecule targeting PD-1 (search) and CTLA-4 (search), in patients with gynecologic cancers (search). The regulatory action follows the occurrence of severe safety events that prompted the company to temporarily pause enrollment of new participants.
Safety Events Trigger Regulatory Action
The FDA's partial clinical hold was initiated after MacroGenics notified the agency of recent safety events across four patients in the study. These events included Grade 4 thrombocytopenia (search) in two patients, Grade 4 myocarditis (search) in one patient, and Grade 4 neutropenia (search) with concurrent septic shock (search) in one patient, which resulted in a Grade 5 event (death).
To date, 41 study participants have been dosed with lorigerlimab at 6 mg/kg every 3 weeks across the platinum-resistant ovarian cancer (search) and clear cell gynecologic cancer (search) cohorts. Under the partial clinical hold, no new patients will be enrolled in the LINNET study until the FDA lifts the hold, though current study participants may continue to receive the study drug.
"At MacroGenics, our top priority is patient safety," said Eric Risser, President and CEO. "MacroGenics is fully committed to working closely with the FDA to resolve the partial clinical hold and we intend to resume study enrollment as soon as possible."
Study Design and Objectives
The LINNET study is evaluating lorigerlimab as monotherapy in a Simon two-stage trial design for eligible patients with platinum-resistant ovarian cancer (search) who have received up to three prior lines of therapy. If a predefined activity threshold is met in the first stage based on approximately 20 patients, the study may expand to enroll an additional 20 patients.
The study was also designed to enroll up to 20 patients with clear cell gynecologic cancer (search) who have received at least one prior line of therapy. The primary endpoint is objective response rate, with multiple secondary endpoints being evaluated.
Bispecific DART Technology Platform
Lorigerlimab represents MacroGenics' proprietary bispecific DART (Dual-Affinity Re-Targeting) molecule technology, which simultaneously targets both PD-1 (search) and CTLA-4 (search) immune checkpoints. The company generates its pipeline of product candidates primarily from its proprietary suite of next-generation antibody-based technology platforms, which have applicability across broad therapeutic domains.
MacroGenics' combination of technology platforms and protein engineering expertise has enabled the company to generate promising product candidates and enter into several strategic collaborations with global pharmaceutical and biotechnology companies.