FDA Halts New Enrollment in MacroGenics’ Lorigerlimab Trial Over Safety Events

MacroGenics, Inc. a clinical-stage biopharmaceutical company specializing in antibody-based cancer therapies, announced that the U.S. Food and Drug Administration (FDA) has placed a partial clinical hold on its ongoing Phase 2 LINNET study. The study investigates lorigerlimab, an investigational bispecific DART® molecule targeting PD-1 and CTLA-4, in patients with gynecologic cancers.

Under the partial hold, enrollment of new patients is suspended until the FDA lifts it. Existing participants 41 patients dosed to date at 6 mg/kg every three weeks across platinum-resistant ovarian cancer (PROC) and clear cell gynecologic cancer (CCGC) cohorts may continue receiving the study drug. This measure prioritizes safety while allowing current treatment to proceed.

The hold stems from MacroGenics’ recent notification to the FDA about a temporary enrollment pause triggered by serious safety events in four patients:

• Grade 4 thrombocytopenia (two cases)
• Grade 4 myocarditis (one case)
• Grade 4 neutropenia with concurrent septic shock (one case, resulting in a fatal Grade 5 event)

These adverse events, occurring amid early dosing in the trial, prompted swift action to assess risks.

LINNET Study Design and Objectives

The LINNET trial follows a Simon two-stage design for lorigerlimab monotherapy. It enrolls PROC patients with up to three prior lines of therapy; the first stage targets about 20 patients, potentially expanding by 20 more if activity thresholds are met. Up to 20 CCGC patients with at least one prior line are also included. The primary endpoint is objective response rate (ORR), supported by secondary measures like duration of response and safety.

Lorigerlimab’s bispecific mechanism simultaneously blocking PD-1 (a key immunotherapy checkpoint) and CTLA-4 (which regulates T-cell activation) aims to enhance anti-tumor activity in hard-to-treat gynecologic cancers, building on the rationale for dual checkpoint inhibition.

MacroGenics’ Response and Path Forward

“Our top priority is patient safety,” stated Eric Risser, President and CEO of MacroGenics. The company is collaborating closely with the FDA to address the hold, with plans to resume enrollment promptly upon resolution.

Partial holds like this are common in oncology trials for investigational immunotherapies, where immune-related adverse events (irAEs) such as myocarditis, cytopenias, and infections can arise due to heightened immune activation. MacroGenics’ proactive pause and transparency underscore standard regulatory practices to mitigate risks in Phase 2 development.

Reference

MacroGenics Announces Pausing of Enrollment of New Study Participants in LINNET Trial, 23 February 2026, https://ir.macrogenics.com/news-releases/news-release-details/macrogenics-announces-pausing-enrollment-new-study-participants