MacroGenics reports 25% response in clear cell gynecologic cancer trial

A 25 per cent confirmed response rate emerged in advanced clear cell gynecologic cancer as MacroGenics, Inc. NASDAQMGNX reported interim Phase 2 LINNET results on Monday. The company is enrolling 20 additional patients at a lower dose, with updated results expected in the first half of 2027.

The Oct. 26 release reported four confirmed responses among 16 response-evaluable clear cell patients at the Sept. 1 cutoff. Across the broader safety population, severe treatment-related adverse events occurred in 49 per cent of patients, including one fatal event in the separate platinum-resistant ovarian cancer cohort.

MacroGenics is a small Maryland biotechnology company developing antibody-based cancer treatments. Its investigational lorigerlimab targets the immune checkpoints PD-1 and CTLA-4 within a single molecule.

Ahead of Monday's announcement, MacroGenics shares closed at US$2.25 on Nasdaq at 4:00 p.m. EDT on Oct. 23, according to NASDAQMGNX. That closing price predates the interim results.

Lower Dose Follows Safety Changes

LINNET's primary endpoint is objective response rate, and the open-label study has no control group. The ESMO poster describes separate cohorts for clear cell disease and high-grade serous platinum-resistant ovarian cancer, so the results do not establish an advantage over another treatment.

The reported safety analysis covered 41 patients receiving intravenous lorigerlimab at 6 milligrams per kilogram every three weeks. They included 17 with clear cell disease and 24 with platinum-resistant ovarian cancer.

The poster explains why total enrolment was higher: another patient had received the lower dose but was excluded from the presented summaries because data were limited. The platinum-resistant ovarian cohort did not proceed to its second stage because of futility.

Among the clear cell patients, disease control reached 44 per cent, or seven of the 16 response-evaluable patients. All four responses remained ongoing at the cutoff.

Median progression-free survival was 2.9 months in the clear cell safety population. Its 95 per cent confidence interval ran from 1.9 to 6.2 months, while the six-month progression-free survival rate was 33 per cent.

Treatment-related adverse events caused discontinuation in 24 per cent of the overall safety population. The corresponding rate in clear cell patients was 18 per cent.

The FDA removed a partial clinical hold on April 8, according to MacroGenics' account. New patients would enter under a revised protocol adding measures to mitigate potential blood and cardiac toxicities; removal of the hold was not marketing approval.

“We believe these data support the promise of dual PD-1/CTLA-4 blockade and lorigerlimab’s potential to improve the treatment paradigm for this underserved patient population,” MacroGenics chief executive Eric Risser said in the release.

Read more: BioNTech reports modest Phase 3 breast-cancer benefit and lung toxicity

Antibody Developers Face Dose Decisions

A broader antibody-development peer, Xencor, Inc. NASDAQXNCR, reported on Oct. 25 five confirmed responses among 11 evaluable kidney-cancer patients at its selected XmAb819 dose. That study involves a different cancer and mechanism, so its response rate cannot establish relative efficacy against lorigerlimab.

Read more: Xencor reports 45.5 per cent confirmed response at selected kidney-cancer dose

For broader sector context, the iShares Biotechnology ETF NASDAQIBB closed at US$207.74 at 4:00 p.m. EDT on Oct. 23.

MacroGenics reported on Aug. 13 cash, equivalents and marketable securities of US$173.3 million at June 30. Its pro forma balance was US$327 million after including manufacturing-sale proceeds and partner payments, with funding projected through 2028.

The next LINNET update is expected in the first half of 2027. Results from the cohort receiving 3 milligrams per kilogram every three weeks will test whether activity persists at the lower dose and clarify tolerability.