Volastra Therapeutics announced it has dosed the first patient in its Phase Ib clinical trial evaluating sovilnesib for patients with platinum-resistant or refractory high-grade serous ovarian cancer (HGSOC). The trial (NCT06084416) is designed as a randomized dose optimization study to establish the recommended Phase 2 dose of once-daily oral sovilnesib.
The U.S. Food and Drug Administration (FDA) has granted Fast Track designation for sovilnesib in this indication, recognizing both the promising initial clinical data and the significant unmet need in this patient population. Volastra in-licensed sovilnesib (formerly AMG-650) from Amgen in February 2023.
Trial Design and Patient Population
The Phase Ib study employs an adaptive multi-cohort design to evaluate tolerability, safety, pharmacokinetics, and efficacy of sovilnesib at various dose levels. The trial is structured in two parts: part one will enroll ten subjects per dose level to collect preliminary data, while part two will expand to include 20 to 30 additional subjects across selected dose levels to finalize the recommended Phase 2 dose.
Dr. Joyce Liu, Associate Chief and Director of Clinical Research in the Division of Gynecologic Oncology at Dana Farber Cancer Institute and a principal investigator on the trial, emphasized the critical need for new treatment approaches: "Patients with advanced HGSOC have poor treatment response rates after disease progression on platinum-based chemotherapy, and as a result have a significant need for new treatment options. We are excited to participate in this trial evaluating a unique treatment approach in hopes of advancing new options for patients."
In the United States alone, more than 20,000 new cases of ovarian cancer are diagnosed each year, with over 75% presenting at advanced stages. The majority of these patients will experience disease progression on platinum-based therapy, highlighting the urgent need for novel therapeutic strategies.
Dual KIF18A Inhibitor Strategy
Sovilnesib is one of Volastra's two class-leading, clinical-stage KIF18A inhibitors specifically designed to treat cancers characterized by high levels of chromosomal instability. The company is simultaneously advancing its internally developed KIF18A inhibitor, VLS-1488, in an ongoing Phase 1 clinical trial (NCT05902988).
"Advancing our two chemically differentiated KIF18A inhibitors in parallel Phase 1 clinical trials presents the rare opportunity to efficiently gather comparative clinical data," said Charles Hugh-Jones, M.D., FRCP, Chief Executive Officer at Volastra. "We believe our strategy will allow us to select the first, and potentially best-in-class, medicine for patients to advance to late-stage development for treatment of platinum-resistant or refractory HGSOC."
Biomarker Development and Partnerships
Beyond clinical development of novel therapeutics, Volastra is deploying multiple unique biomarker approaches to measure chromosomal instability and other predictors of response to KIF18A inhibitors. The company has established partnerships with industry leaders including Microsoft, Tailor Bio, and Function Oncology to advance this work.
These biomarker initiatives aim to identify patients most likely to benefit from KIF18A inhibition therapy, potentially enabling more precise treatment selection and improving outcomes in this difficult-to-treat patient population.
About Volastra Therapeutics
Founded in 2019 by Lewis Cantley, Ph.D., Samuel Bakhoum, M.D., Ph.D., and Olivier Elemento, Ph.D., Volastra Therapeutics is a New York-based clinical-stage biotechnology company pioneering novel approaches to treating cancer by targeting chromosomal instability. The company is funded by investors including Polaris Partners, Arch Ventures, Droia Ventures, Vida Ventures, Catalio Capital Management, and Eli Lilly & Company.
In addition to its two clinical-stage KIF18A inhibitors, Volastra maintains a robust discovery pipeline targeting novel approaches to chromosomal instability, both internally and in collaboration with Bristol Myers Squibb. The company's focus on chromosomal instability represents a distinctive approach to cancer treatment that could potentially address significant unmet needs across multiple tumor types.
