Experimental drug shrinks tumors in hard-to-treat cancers
Phase 1 trial data show SIM0505 holds promise for ovarian, uterine cancers
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SIM0505, a treatment being developed by Nextcure and Simcere Zaiming, resulted in partial responses in more than half of patients with hard- to-treat ovarian and uterine cancers, two types of gynecologic cancer, while maintaining a manageable safety profile that supports continued clinical development.
These data come from an open-label Phase 1 clinical study (NCT06792552) evaluating the safety of SIM0505 at increasing doses and how well it works in heavily pretreated adults with advanced solid tumors.
The now-completed dose-escalation part enrolled 59 patients at sites in the U.S. and China and tested doses ranging from 1.6 mg/kg to 9.6 mg/kg. A dose-optimization portion, expected to enroll 120 participants with platinum-resistant ovarian cancer, is testing three dose levels (5.6 mg/kg, 6.4 mg/kg, and 7.2 mg/kg) to determine the optimal dose for a planned pivotal trial.
The data were presented at the American Society for Clinical Oncology 2026 conference, held June 4-8 in Chicago, in a poster titled, “Phase I, Multicenter, first-in-human (FIH) global study of SIM0505, an anti-CDH6 antibody-drug conjugate (ADC) in patients with advanced solid tumors.”
“We believe SIM0505 has broad potential in gynecologic cancers and beyond, and these data put us on a solid track toward pivotal studies and our goal of bringing this treatment to patients,” Michael Richman, president and CEO of Nextcure, said in a company press release. Nextcure owns global rights to SIM0505, except in China, Hong Kong, Macau, and Taiwan, where rights remain with Simcere.
Protein-targeting treatment aims for ‘deeper, more durable response’
Ovarian cancer and uterine serous carcinoma are challenging to treat and often come with a poor prognosis. Ovarian cancer is commonly treated with platinum-based chemotherapy, but once resistance to platinum therapies develops, only about 10%-25% of patients respond to available therapies, and median survival is about 11 months.
Uterine serous carcinoma is rarer, accounting for about one in 10 uterine cancers, but its aggressiveness makes it responsible for about 40% of uterine cancer deaths.
SIM0505 is designed to target CDH6, a protein found on some cancer cells, including ovarian, uterine, and endometrial cancers. Once bound to CDH16, the therapy is taken up by the cancer cells and delivers a toxic payload, a proprietary topoisomerase 1 inhibitor, that kills the cells.
“Treatment of gynecologic cancers has advanced meaningfully in recent years, yet the need for safer and more effective treatments remains real,” said Udayan Guha, MD, PhD, chief medical officer of Nextcure. “CDH6 is an attractive target given its expression across ovarian, uterine, and other solid tumors. ADCs directed at this target have the potential to deliver the deeper, more durable responses these patients need.”
SIM0505 has received fast track designation from the U.S. Food and Drug Administration (FDA) to treat platinum-resistant ovarian cancer, which is expected to help speed its development for patients with this difficult-to-treat cancer.
The dose-escalation portion of the Phase 1 study was designed to evaluate the safety, tolerability, pharmacological properties, and preliminary signs of efficacy of multiple dose levels of SIM0505 in people with advanced solid tumors.
Of the 59 patients included in this part, 46 had ovarian cancer, 10 had uterine serous carcinoma or other type of endometrial cancer (a type of cancer that grows from cells in the lining of the uterus), and three had renal cell cancer (a type of kidney cancer).
Treatment was administered by infusion every 21 days. As of April, participants had been followed for a median of 5.2 months.
Responses to treatment were assessed in people with gynecologic cancers who had received therapeutic doses of 4.8 mg/kg–8.0 mg/kg and had been followed for at least 12 weeks. Of 20 patients in this group, 11 responded partially to treatment, meaning their tumors shrank, and many had evident responses as early as six weeks after their first infusion. This translated into an objective response rate of 55%.
Nine of 17 people (52.9%) with ovarian cancer experienced a partial response, as did two of three (66.7%) with uterine serous carcinoma.
SIM0505’s safety and tolerability profile was “manageable,” researchers wrote in the poster. Most side effects were mild to moderate and mainly included low numbers of blood cells or blood-clotting platelets, nausea, and vomiting. Three patients stopped treatment due to side effects, and 12 had to reduce their dose.
“Meaningful response rates at 12 weeks, alongside a manageable safety profile, give us strong confidence in this program and reinforce our enthusiasm for the ongoing dose optimization study,” Richman said.
Renhong Tang, PhD, CEO of Simcere Zaiming, said the “results validate the science behind the SIM0505 construct and the accelerating pace of the global development program. Together with our partner, we remain deeply committed to advancing innovative medicines for patients facing hard-to-treat cancers.”
