FDA Grants Fast Track Designation to ADC for Platinum-Resistant Ovarian Cancer

The FDA has granted fast track designation to the investigational antibody-drug conjugate (ADC) SIM0505 for the treatment of women with platinum-resistant ovarian cancer. The designation adds SIM0505 to a growing class of CDH6-targeted agents under investigation in this difficult-to-treat population.¹

SIM0505 is a novel CDH6-directed ADC featuring a proprietary topoisomerase I inhibitor payload. The agent is designed to achieve broad antitumor activity with fast systemic clearance and an improved potential therapeutic window. It is currently being evaluated in an open-label phase 1 study (NCT06792552) in patients with advanced solid tumors, with a particular emphasis on platinum-resistant ovarian cancer.

“Securing fast track designation for SIM0505 validates the urgent, unmet need for new treatments for platinum resistant ovarian cancer and enables us to work more closely with FDA to accelerate development. We believe this designation will help to streamline and de-risk development through proactive and ongoing engagement with FDA,” Michael Richman, president and CEO of NextCure, the developer of the ADC, stated in a news release.¹ 

“We are committed to bringing SIM0505 to patients as quickly as possible and we plan to initiate dose optimization in ovarian cancer patients in the second quarter of 2026. In addition, we look forward to presenting phase 1 data on the program at the upcoming 2026 American Society of Clinical Oncology conference,” added Richman.

Treatment Context and Phase 1 Study Design

Platinum-resistant ovarian cancer remains one of the most clinically challenging settings in gynecologic oncology. CDH6 is overexpressed in approximately 65% to 85% of ovarian cancer patients and is associated with poor prognosis, making it an attractive target for ADC-based approaches.

The first-in-human, open-label, multicenter phase 1 trial of SIM0505 is underway to assess the safety profile, tolerability, pharmacokinetic characteristics, and early signals of antitumor efficacy of the ADC in adults with advanced solid malignancies.² The study design includes both a dose-escalation stage and a subsequent dose-optimization stage.

In the escalation phase, a range of dose levels is being tested to identify the maximum tolerated dose as well as the dose recommended for expansion. The optimization phase will further examine approximately 2 to 3 selected dose levels to better define the therapeutic index, with a focus on cohorts including ovarian cancer, renal cell carcinoma, non–small cell lung cancer, and uterine cancer. SIM0505 is administered intravenously on a once-every-21-day schedule.

Eligible participants must be at least 18 years of age with histologically or cytologically confirmed advanced solid tumors that have either progressed following at least 1 prior systemic anticancer therapy or lack available standard treatment options. Patients are also required to have at least 1 measurable lesion according to RECIST v1.1 criteria. For inclusion in the PROC-specific cohort, individuals must have high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.

Key exclusion criteria include symptomatic central nervous system metastases, prior noninfectious pneumonitis requiring corticosteroid treatment, active infections necessitating intravenous systemic therapy within 2 weeks before study initiation, or a history of bowel obstruction within 3 months before receiving the first dose.

The primary outcomes for the dose-escalation phase include the incidence of dose-limiting toxicities and treatment-emergent adverse events, whereas the main endpoint in the dose-optimization phase is objective response rate.

The study is enrolling patients at 17 locations across the United States and China. United States locations include sites in Florida, Georgia, Louisiana, Massachusetts, New Jersey, New York, Tennessee, and Texas. The targeted enrollment of the study is over 400 patients. The estimated primary completion date of the phase 1 trial is February 2028.

REFERENCES

1. NextCure receives Fast Track designation for SIM0505 (CDH6 ADC). News release. Published April 7, 2025. Accessed April 8, 2026. https://tinyurl.com/rnuby4jf

2. ClinicalTrials.gov. A study of SIM0505 in participants with advanced solid tumors (NCT06792552). January 29, 2026. Accessed April 8, 2026. https://clinicaltrials.gov/study/NCT06792552