Volastra Therapeutics has announced promising preliminary results from its first-in-human Phase I/II trial of VLS-1488, a novel oral KIF18A inhibitor, showing tumor reduction in patients with heavily pre-treated advanced ovarian cancer. These findings will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting on June 2.
The dose escalation portion of the trial enrolled 52 patients with advanced solid tumors across dose levels ranging from 50 mg to 800 mg. As of the January 10, 2025 data cutoff, the drug demonstrated a favorable safety profile with no dose-limiting toxicities observed and no maximum tolerated dose reached. Less than 45% of patients experienced treatment-related adverse events (TRAEs) of any grade, and fewer than 16% experienced Grade 3 TRAEs. Notably, no patients experienced adverse events greater than Grade 3.
"We are excited by these results from our VLS-1488 KIF18A inhibitor program, demonstrating a favorable safety profile at clinically active doses, with tumor shrinkage in patients with heavily pre-treated ovarian cancer," said Scott Drutman, M.D., Ph.D., Chief Medical Officer and Head of R&D of Volastra Therapeutics. "These initial data represent a major milestone for the field of chromosomal instability and provide a clear path for dose and patient population selection for the next phase of development."
Promising Efficacy in Ovarian Cancer Patients
Among the 20 patients with advanced high-grade serous ovarian cancer enrolled in the trial, most were platinum-resistant and heavily pretreated, with a median of 5 prior lines of therapy. Of the 17 response-evaluable patients, 7 demonstrated a reduction in tumor size, including 3 partial responses according to RECIST criteria. Five patients remained on therapy at the time of data cutoff.
Ecaterina Dumbrava, M.D., Assistant Professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center and investigator on the trial, commented: "These early data show VLS-1488 to be very well tolerated, with promising initial efficacy in ovarian cancer. The data that will be presented demonstrate the potential of KIF18A as a novel, relevant therapeutic target for hard-to-treat cancers and I look forward to continued development."
Novel Mechanism Targeting Chromosomal Instability
VLS-1488 is an oral small molecule inhibitor of KIF18A, a kinesin protein essential for cancer cell division and a synthetic lethal target in chromosomally unstable cancers. The drug received Fast Track Designation from the FDA in October 2024 for treating patients with platinum-resistant high-grade serous ovarian cancer.
High-grade serous ovarian cancer accounts for approximately 75% of all ovarian cancers and about 80% of all ovarian cancer deaths. It is almost universally chromosomally unstable, making it a prime candidate for therapies targeting this mechanism.
In the United States alone, more than 20,000 new cases of ovarian cancer are diagnosed each year, with over 75% being advanced at diagnosis. Most of these patients will experience disease progression on platinum-based therapy, highlighting the significant unmet need for new treatment approaches.
Ongoing Clinical Development
The Phase I/II trial (NCT05902988) is evaluating the safety, tolerability, pharmacokinetics, and antitumor activity of VLS-1488 in patients with advanced solid tumors, including high-grade serous ovarian cancer. The study consists of two parts: Dose Escalation and Dose Expansion. Enrollment in the dose expansion portion is currently ongoing.
Volastra continues to explore the broad potential of its two KIF18A inhibitors, VLS-1488 and sovilnesib (formerly AMG-650), in ovarian and other cancers. Both assets are currently being evaluated in Phase I clinical trials for platinum-resistant ovarian cancer and other advanced solid tumors.
About Volastra Therapeutics
Volastra Therapeutics is a clinical-stage biotechnology company pioneering novel approaches to cancer treatment by targeting chromosomal instability. Founded in 2019 by Lewis Cantley, Ph.D., Samuel Bakhoum, M.D., Ph.D., and Olivier Elemento, Ph.D., the company is developing new techniques to understand the biology of chromosomal instability and leveraging these insights to drive forward a preclinical pipeline of therapies against innovative targets.
The company is funded by key investors including Polaris Partners, ARCH Ventures, B-Capital, Droia Ventures, Vida Ventures, Catalio Capital Management, and Eli Lilly & Company. Notable partners include Tailor Bio and Microsoft.
The detailed results from this trial will be presented at the ASCO Rapid Oral Abstract Session titled "Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology – Small Molecules" on Monday, June 2, 2025, from 8:00 AM to 9:30 AM CT at the McCormick Place Convention Center, S406.
