Patient Death Forces Partial Freeze on MacroGenics’ Gynecologic Cancer Study

 

A trial of a MacroGenics’ drug temporarily paused enrollment after several safety events, including a fatality. The deceased patient had developed a severe case of neutropenia and concurrent septic shock.

A patient has died in a mid-stage study of MacroGenics’ bispecific antibody lorigerlimab in gynecologic cancers, prompting the FDA to slap a partial clinical hold on the trial.

The patient in question developed grade 4 neutropenia and concurrent septic shock, the biotech reported in its Tuesday news release. MacroGenics also disclosed three other grade 4 events: one episode of myocarditis and two cases of thrombocytopenia. Grade 4 safety events are defined as those that are life-threatening and require urgent intervention.

At $1.60 apiece when markets opened on Tuesday, MacroGenics’ stock price fell some 8% from its previous closing price of $1.75. The biotech has since recovered much of its share value, closing Tuesday’s session at $1.73.

“Our top priority is patient safety,” CEO Eric Risser said in a prepared statement. MacroGenics had previously temporarily paused enrollment in the Phase 2 trial after detecting the safety signals. The company will work with the FDA toward lifting the hold and resuming the study “as soon as possible,” Risser added.

Patients already enrolled in the trial can continue treatment, the biotech said in its Tuesday release. So far, 41 patients have been dosed.

Lorigerlimab is a bispecific antibody that works by targeting both the PD-1 and CTLA-4 proteins to boost the body’s anticancer activity and prevent malignant cells from evading the immune response.

MacroGenics is testing the antibody in the Phase 2 LINNET study, which aims to enroll around 60 patients with platinum-resistant ovarian cancer or clear cell gynecologic cancer. The biotech is also running a mid-stage trial of lorigerlimab in metastatic castration-resistant prostate cancer and a Phase 1 study in unresectable or metastatic advanced solid tumors.

With its mechanism of action, lorigerlimab joins a growing class of anticancer therapies that target two disease pathways simultaneously—though MacroGenics’ approach helps set lorigerlimab apart.

The space is currently led by Summit Therapeutics’ ivonescimab, which in September 2024 beat Merck’s Keytruda in a Chinese non-small cell lung cancer study. The therapy has since run into some cross-country survival data issues, but is nevertheless under FDA review, with a target action date of Nov. 14, 2026.

Also in this space are BioNTech, which in June last year attracted an $11 billion investment from Bristol Myers Squibb for its own bispecific BNT327, and Pfizer, which partnered with China’s 3SBio in May 2025 for up to $6 billion.

These players, however, are targeting the PD-1 and VEGF pathways, giving MacroGenics a point of differentiation since lorigerlimab acts on the CTLA-4 cascade. Akeso, Summit’s Chinese partner, has a similar asset in cadonilimab, for which it is running a late-stage program in gastric cancer.

https://www.biospace.com/drug-development/patient-death-forces-partial-freeze-on-macrogenics-gynecologic-cancer-study