Study of NKT3964 in gynecological, other cancers advances
Phase 1 trial to enroll up to 90 adults with advanced, metastatic solid tumors
A Phase 1 clinical trial testing Nikang Therapeutics’ oral therapy NKT3964 in people with certain advanced or metastatic solid tumors, including gynecological cancers, has completed dosing the first group of patients.
The Phase 1 study (NCT06586957) is estimated to enroll up to 90 adults with advanced or metastatic solid tumors that are linked to higher than normal levels of cyclin E, a protein that promotes cell growth by binding to CDK2, the target of NKT3964. Recruitment may still be open at its three U.S. sites.
“We are thrilled to reach this milestone in the clinical development of NKT3964,” Zhenhai Gao, PhD, co-founder, president, and CEO of Nikang, said in a company press release. “Completing dosing in our first [patient group] brings us one step closer to understanding the potential of this groundbreaking CDK2 degrader, one of several molecules in our portfolio targeting the cell cycle.”
Early pharmacological data from this first group “demonstrated good oral exposure” and “CDK2 degradation levels” that align with the company’s projections based on preclinical studies, Gao said. CDK2, which stands for cyclin-dependent kinase 2, is an enzyme involved in regulating cell growth through complex interactions with other proteins, including cyclin E. The abnormal activation of the CDK2/cyclin E complex is thought to contribute to the growth of several advanced cancers including ovarian, endometrial, lung, and gastric cancers.
NKT3964 is designed to potently and selectively break down CDK2, resulting in prolonged CDK2 pathway suppression without cyclin E accumulation. It’s part of a class of molecules called proteolysis-targeting chimeras, or PROTACs, that harness cells’ protein degradation machinery to break down a target protein.
Evaluating NKT3964
According to the company, preclinical studies demonstrated that the therapy suppressed the growth of CDK2-dependent cancer cells, while sparing healthy ones. Also, in animal models of tumors marked by high cyclin E, NKT3964 was shown to break down CDK2 in a dose-dependent way, while reducing tumor growth.
The ongoing Phase 1 trial is evaluating NKT3964’s safety, pharmacological properties, and preliminary efficacy in adults with advanced or metastatic ovarian, endometrial, gastric, and other solid tumors with signs of high cyclin E. Adults with certain types of advanced or metastatic lung and breast cancer in which high cyclin E levels have been associated with poor outcomes are also eligible.
In its first, dose-escalation part, the participants are receiving increasing doses of NKT3964 to determine the maximum tolerated dose, or highest dose that doesn’t cause unacceptable side effects. Data from this part will help determine two recommended doses for the trial’s dose-expansion part, which will feature a larger group of patients, including those with platinum-resistant ovarian cancer and evidence of high cyclin E levels.
Initial data from the first group suggested good NKT3964 levels with oral administration, achieving a desirable CDK2 degradation consistent with data from preclinical studies, according to the company.
“These early observations are particularly encouraging as they address the considerable challenges of achieving oral bioavailability with a PROTAC degrader,” Gao said. “These findings will help guide dose optimization as the trial advances. We are excited by this progress and remain committed to advancing transformative therapies to help patients fight cancer and live better lives.”
