FDA Pauses Lorigerlimab Study in Gynecologic Cancers After Patient Death

The U.S. Food and Drug Administration (FDA) has placed a partial clinical hold on MacroGenics’ mid-stage study of lorigerlimab in gynecologic cancers after a patient died from severe side effects, the company announced Tuesday. The hold follows several serious safety events, including a fatal case of grade 4 (life-threatening) neutropenia with concurrent septic shock, and affects enrollment in the ongoing trial.

MacroGenics reported that the patient developed grade 4 neutropenia, a life-threatening drop in white blood cells, along with septic shock. Grade 4 side effects are defined as life-threatening and requiring urgent medical intervention. In response to these safety signals, the company temporarily paused enrollment in the study before the FDA issued the partial hold.

According to the company, patients who are already enrolled in the trial may continue receiving treatment. So far, 41 patients have been dosed in the study.

“Our top priority is patient safety,” CEO Eric Risser said in a prepared statement. He added that MacroGenics will work with the FDA to lift the hold and resume the study as soon as possible.

What happened in the lorigerlimab study?

In addition to the fatal case of grade 4 neutropenia and septic shock, MacroGenics disclosed three other grade 4 side effects in the trial. These included one episode of myocarditis, which is inflammation of the heart muscle, and two cases of thrombocytopenia, a condition marked by dangerously low platelet levels that can increase bleeding risk.

Grade 4 side effects are considered the most severe category short of death and require urgent medical care.

The safety concerns emerged during a phase 2 trial evaluating lorigerlimab in patients with certain gynecologic cancers. Following detection of these events, the company paused enrollment before the FDA’s partial clinical hold was announced.

Despite the hold on new enrollment, treatment may continue for patients who are already participating in the trial.

Lorigerlimab is a bispecific antibody designed to target both PD-1 and CTLA-4, two proteins involved in regulating the immune system. By targeting these proteins, the drug is intended to enhance the body’s anticancer immune response and help prevent malignant cells from evading immune detection.

What is the LINNET trial testing?

Lorigerlimab is being studied in the phase 2 LINNET trial, which aims to enroll approximately 60 patients with platinum-resistant ovarian cancer or clear cell gynecologic cancer. Platinum-resistant ovarian cancer refers to disease that does not respond to or returns shortly after platinum-based chemotherapy.

The study is considered mid-stage and is focused on evaluating the therapy in patients with limited treatment options.

In addition to the LINNET study, MacroGenics is conducting a separate mid-stage trial of lorigerlimab in metastatic castration-resistant prostate cancer. The company is also running a phase 1 study in patients with unresectable or metastatic advanced solid tumors.

Lorigerlimab belongs to a growing class of anticancer therapies known as bispecific antibodies, which are engineered to target two different biological pathways at the same time. In this case, lorigerlimab acts on the PD-1 and CTLA-4 pathways. According to the company, its mechanism helps distinguish it from other investigational therapies that target PD-1 in combination with VEGF.

What patients should know about side effects and next steps

The partial clinical hold means that new patients cannot currently enroll in the LINNET trial. However, those already receiving lorigerlimab in the study may continue treatment while the company works with the FDA to address safety concerns.

A partial hold is typically issued when regulators determine that additional safety evaluation is needed before a trial can proceed as planned.

MacroGenics has stated that it will collaborate with the FDA in an effort to lift the hold and resume enrollment as soon as possible.

The company disclosed that 41 patients have received lorigerlimab in the LINNET trial to date. The reported grade 4 side effects — including neutropenia, septic shock, myocarditis and thrombocytopenia — are considered life-threatening and require urgent medical intervention.

Patients currently participating in the study are encouraged to speak with their health care team about any questions regarding treatment continuation and monitoring.

References

1. “Patient Death Forces Partial Freeze on MacroGenics’ Gynecologic Cancer Study.” BioSpace. News Release.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI, reviewed by a human editor, but not independently verified by a medical professional.

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