FDA Lifts Partial Clinical Hold on Lorigerlimab for Gynecologic Cancer

The FDA has removed the partial clinical hold on the phase 2 LINNET study (NCT06730347) evaluating lorigerlimab in patients with gynecologic cancers, according to a news release from MacroGenics.¹ Lorigerlimab is an investigational, bispecific DART molecule designed to simultaneously target PD-1 and CTLA-4. The removal of the hold follows a comprehensive review of safety data and the implementation of a revised study protocol designed to mitigate specific risks.

The decision allows the trial to resume enrollment of new participants following a pause initiated in February 2026.² The hold was initially placed due to the occurrence of recent serious safety events among new patients, including 2 cases of grade 4 neutropenia and 1 case of grade 4 myocarditis, as well as 1 patient who experienced grade 4 neutropenia and concurrent septic shock, which led to a grade 5 fatal event. Under the hold, new patients were no longer enrolled in the trial, though patients who were already enrolled were permitted to continue receiving treatment.

With the lifting of this partial clinical hold, new patients will be enrolled in the trial once more, only with a revised protocol including additional risk-mitigation strategies for potential hematologic and cardiac toxicities.

“We are grateful for the productive interaction with the reviewers at the FDA’s Office of Oncologic Diseases, as well as the diligent efforts of the MacroGenics team to provide a rapid and comprehensive response to the FDA,” said Eric Risser, president and chief executive officer of MacroGenics, in the press release.¹ “With the partial clinical hold lifted, we intend to resume enrollment of new study participants in the ongoing LINNET study and we remain on track to provide a mid-year clinical update on the program.”

How is the Phase 2 LINNET Trial Structured?

While the primary analysis for the phase 2 LINNET trial is ongoing, the study is designed to evaluate the objective response rate (ORR) as the primary end point. Secondary outcomes include duration of response, progression-free survival, and overall survival. To date, 41 study participants have been dosed across the 2 evaluation cohorts, which consist of patients with platinum-resistant ovarian cancer or clear cell gynecologic cancer who have received at least 1 prior line of therapy.

The developer expects to report an initial clinical data update from the LINNET study in the second half of 2026, which will provide further insight into the agent's efficacy in platinum-resistant and clear cell gynecologic malignancies.

The LINNET study is an open-label, multicenter trial evaluating lorigerlimab as a monotherapy in patients with either platinum-resistant ovarian cancer or clear cell gynecologic cancer.³ The treatment regimen consists of lorigerlimab administered intravenously once every 21 days.

All participants will be monitored closely for toxicity by physical exam and routine laboratory tests every cycle, and tumor status will be checked approximately every 9 weeks for the first year, then every 12 weeks for the duration of treatment. Additionally, a safety follow-up will be performed within 30 days of treatment discontinuation, and those who discontinue study treatment for reasons other than progression of cancer will continue CA-125 and tumor assessments every 12 weeks.

Eligible patients for the PROC cohort must have received between 1 and 3 prior lines of systemic therapy and demonstrated disease resistance to platinum-based regimens. For the CCGC cohort, patients must have received at least 1 prior line of therapy for advanced or recurrent disease. All participants were required to have measurable disease per RECIST v1.1 criteria and acceptable physical condition and laboratory values. Patients previously treated with immune checkpoint inhibitors are generally excluded from the ovarian cancer cohort, although prior use is permitted for certain clear cell endometrial or cervical cancers.

References

1. FDA removes partial clinical hold on MacroGenics’ LINNET study. News release. MacroGenics, Inc. April 8, 2026. Accessed April 9, 2026. https://tinyurl.com/2rnndbfp
2. MacroGenics announces pausing of enrollment of new study participants in LINNET trial. News release. MacroGenics Inc. February 24, 2026. Accessed April 9, 2026. https://tinyurl.com/2uak5zt6
3. A study of lorigerlimab in participants with advanced solid tumors (LINNET). ClinicalTrials.gov. Updated March 5, 2026. Accessed April 9, 2026. https://tinyurl.com/38ckwxz9