NextCure’s anti-CDH6 ADC receives FDA Fast Track designation for platinum-resistant ovarian cancer

NextCure, Inc. (Nasdaq: NXTC), a clinical-stage biopharmaceutical company headquartered in Beltsville, Maryland, announced receipt of US FDA Fast Track Designation for SIM0505, an anti-Cadherin-6 (CDH6) antibody-drug conjugate (ADC) carrying a proprietary topoisomerase 1 inhibitor (TOPOi) payload. The fast-track status is awarded in relation to SIM0505’s potential as a treatment of women with platinum-resistant ovarian cancer (PROC).

Fast Track Designation gives NextCure eligibility for more frequent written and meeting-based interactions with the US FDA, rolling review of application sections, and potential qualification for Priority Review upon submission of a marketing application. No prior expedited designations for SIM0505 have been awarded.

SIM0505 is currently being evaluated in an open-label Phase I study (NCT06792552) enrolling patients with advanced solid tumors, with a stated emphasis on PROC cohorts. The trial expanded into the United States in October 2025 following an initial period of enrollment in China under a collaboration with Simcere Zaiming Pharmaceutical Co., Ltd., which retains rights to SIM0505 in China, Hong Kong, Macau, and Taiwan. NextCure holds exclusive rights in all other markets. Phase I data are scheduled for presentation at the 2026 American Society of Clinical Oncology annual meeting, with dose optimization in ovarian cancer patients expected to begin in Q2 2026.

The ADC is designed to combine fast systemic clearance with broad anti-tumor activity. The TOPOi payload class — shared by several approved and late-stage ADCs — induces DNA single-strand breaks that trigger tumor cell apoptosis. The CDH6 target distinguishes SIM0505 from the majority of ADCs currently in development or approved for ovarian cancer, most of which engage folate receptor alpha (FRα), HER2, or Nectin-4.

Research context

PROC is defined by disease progression within six months of completing platinum-based chemotherapy and carries a median overall survival measured in months with available therapies. The FDA has approved mirvetuximab soravtansine (ImmunoGen’s Elahere) for FRα-high PROC, and several PARP inhibitors are used in maintenance settings for earlier-line disease. Bevacizumab retains a role in combination regimens. Despite these options, patients who progress through multiple lines — or who lack qualifying biomarker expression — have limited alternatives with durable benefit.

CDH6 is a cell-adhesion molecule expressed in ovarian cancer and other solid tumors, and has drawn interest as an ADC target partly because its expression pattern differs from FRα, potentially identifying a patient population not served by mirvetuximab soravtansine.

Unlike FRα-targeted agents such as mirvetuximab soravtansine, which uses a maytansinoid (DM4) payload, SIM0505 employs a TOPOi warhead — the same mechanistic class used by trastuzumab deruxtecan (T-DXd, Daiichi Sankyo/AstraZeneca) and datopotamab deruxtecan, both of which have generated response data in ovarian cancer. Whether SIM0505’s CDH6 targeting combined with a TOPOi payload confers differentiated activity relative to these agents in PROC will depend on clinical data not yet available.

The PROC ADC landscape is becoming crowded at the clinical level. Beyond mirvetuximab soravtansine, multiple CDH6-directed programs are in development globally, while the broader TOPOi-ADC class is being evaluated across numerous gynecologic tumor types. The leading example of another CDH6-targeted ADC is OnCusp Therapeutics’ CUSP06, currently Phase I stage.