FDA Issues Partial Clinical Hold on Lorigerlimab Trial in Gynecologic Cancers

The FDA has placed a partial clinical hold on the phase 2 LINNET study (NCT06730347), which is evaluating lorigerlimab as monotherapy for patients with gynecologic cancers, according to an announcement from MacroGenics, Inc.¹

Under the clinical hold, new patients will no longer be enrolled in the trial. The regulatory action was initiated after the developer notified the FDA of a temporary pause in enrollment due to the occurrence of recent serious safety events among treated patients. While new enrollment is suspended, participants currently enrolled in the study may continue to receive the investigational drug.

The partial clinical hold was prompted by safety events occurring across 4 patients in the study. These events included 2 cases of grade 4 thrombocytopenia and 1 case of grade 4 myocarditis. Additionally, 1 patient experienced grade 4 neutropenia and concurrent septic shock, which subsequently led to a grade 5 fatal event. The company is currently conducting a thorough review of the safety data to determine the next steps for the clinical program.

“At MacroGenics, our top priority is patient safety,” stated Eric Risser, president and chief executive officer of MacroGenics, in the press release.¹ “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.”

The primary end point of the trial is the objective response rate, with secondary end points including incidence of adverse effects (AEs), serious AEs, duration of response, progression-free survival, and disease control rate.

At the time of the enrollment pause, no specific efficacy findings or response percentages were reported. The trial utilized a Simon 2-stage design, which includes a predefined activity threshold in the first stage that must be met to trigger expansion into the second stage of enrollment.

Lorigerlimab is a bispecific DART molecule designed to target both PD-1 and CTLA-4, aiming to enhance the immune system’s ability to recognize and attack tumor cells.

Thus far, 41 patients have been enrolled in the trial and have received a 6 mg/kg dose of lorigerlimab intravenously every 3 weeks. The study consists of 2 distinct patient cohorts. The first cohort focuses on patients with platinum-resistant ovarian cancer (PROC) who have received up to 3 prior lines of therapy. This cohort follows the 2-stage design, with an initial stage of approximately 20 patients and a potential expansion to enroll an additional 20 patients if activity thresholds are met. The second cohort was designed to enroll up to 20 patients with clear cell gynecologic cancer (CCGC) who have received at least 1 prior line of therapy.

Eligible patients for the trial had histologically confirmed high-grade serous epithelial ovarian cancer, including primary peritoneal or fallopian tube cancer, resistant to platinum-based chemotherapy, or histologically confirmed clear cell carcinoma of the ovary, endometrium, vagina, vulva, or cervix.² They also had persistent or recurrent disease with documented disease progression and at least 1 lesion with measurable disease. Previous treatment requirements included between 1 and 3 prior lines of therapy for those with PROC, at least 1 prior line for those with CCGC, and progression on/intolerance to a PARP inhibitor for those with a known BRCA mutation.

References

1. MacroGenics announces pausing of enrollment of new study participants in LINNET trial. News release. MacroGenics, Inc. February 23, 2026. Accessed February 25, 2026. https://tinyurl.com/2uak5zt6
2. A study of lorigerlimab in participants with advanced solid tumors. ClinicalTrials.gov. Updated November 12, 2025. Accessed February 25, 2026. https://tinyurl.com/2c55mrhh