FDA Grants Fast Track Designation to VLS-1488 For Patients With Platinum-Resistant HGSOC

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The FDA has granted a fast track designation to VLS-1488 (Volastra Therapeutics) for the treatment of patients with platinum-resistant high-grade serous ovarian cancer (HGSOC). VLS-1488 is currently being evaluated in the phase 1/2 clinical trial (NCT05902988) to determine its safety, tolerability, and preliminary efficacy in patients who have advanced tumors, including those with HGSOC.¹

VLS-1488 is an internally discovered KIF18A inhibitor. KIF18A is a protein that guides cells through mitosis by helping to align chromosomes, and the inhibitor traps chromosomally unstable tumor cells while in mitosis. This action prevents the cells from proliferating and will lead to cell death, with normal and healthy cells experiencing minimal effects. Because of the inhibitor’s selective abilities, the investigators believe that it will be effective against tumor cells and tolerated by normal cells without imposing toxic effects on normal cells.^1,2

The clinical trial (NCT05902988) evaluating VLS-1488 is the first-in-human phase 1/2 study to evaluate the safety, efficacy, and preliminary efficacy of VLS-1488 in patients with advanced cancers, such as HGSOC. The trial consists of 2 parts: dose escalation and dose expansion. The dose escalation will examine the safety and tolerability of VLS-1488 in different solid tumor types at various dose levels through a series of dose escalation and backfill cohorts to determine the maximum tolerated dose (MTD) as well as select dose levels for dose expansion. The dose expansion portion will examine the safety, tolerability, drug-drug interaction risk, food effect, and preliminary efficacy of VLS-1488 in different tumor types and/or dose levels of interest through multiple expansion cohorts.³

All patients enrolled in the trial were at least 18 years of age, had an ECOG performance status of 1 or below, at least 1 site of measurable disease evaluable by CT scan or MRI, and able to take oral medication without alteration. Eligible tumor types include the following: high grade serous ovarian, fallopian tube, or primary peritoneal cancer; squamous non-small cell lung cancer; triple-negative breast cancer; gastric adenocarcinoma; gastroesophageal cancer; esophageal cancer; colorectal adenocarcinoma; transitional cell carcinoma of bladder; head and neck squamous cell carcinoma; ovarian or uterine carcinosarcoma; and uterine serous carcinoma. Additionally, the dose escalation phase of the study required patients to have no available therapeutic options to provide clinically meaningful benefits in certain cancer types. The dose expansion requires patients to have been previously treated with several lies of standard of care treatment specified in the protocol in their cancer type.^3,4

All the enrolled participants were treated with oral VLS-1488 tablets once per day in 28-day cycles. In the dose escalation phase, primary end points include incidence of dose limiting toxicities, MTD, frequency of serious adverse events (AEs) and treatment-related AEs, and frequency of dose interruptions or discontinuations, all of which will be assessed up to 12 months. Primary end points of the dose expansion phase include objective response rate and frequency of trigger events, which will be assessed up to 18 months. Secondary end points in both phases include duration of response, disease control rate, progression-free survival (which will be evaluated up to 32 months), among others.³

“Platinum-resistant HGSOC is marked by poor prognosis, highlighting the urgent need for new therapies for this devastating disease,” Scott Drutman, MD, PhD, CMO, and head of research and development Volastra Therapeutics, said in a news release. “Fast track designation for VLS-1488 reaffirms the clear potential of KIF18A inhibition to address this unmet medical need and represents a critical step towards bringing these novel therapeutics to patients. We look forward to working closely with the FDA as we advance the development of inhibitors against this promising target.”¹

REFERENCES

1. Businesswire. Volastra Therapeutics Granted FDA Fast Track Designation for Novel KIF18A Inhibitor in Ovarian Cancer. News release. October 2, 2024. Accessed October 2, 2024. https://www.businesswire.com/news/home/20241002653121/en/Volastra-Therapeutics-Granted-FDA-Fast-Track-Designation-for-Novel-KIF18A-Inhibitor-in-Ovarian-Cancer

2. Volasatra. A closer look at Volastra’s lead program: KIF18A inhibitor. News release. September 29, 2022. Accessed October 2, 2024. https://www.volastratx.com/a-closer-look-at-volastras-lead-program-kif18a-inhibitor/

3. A Phase I/​II Study of VLS-1488 in Subjects with Advanced Cancer. ClinicalTrials.gov identifier: NCT05902988. Updated September 19, 2024. Accessed October 2, 2024. https://clinicaltrials.gov/study/NCT05902988

4. Gaillard S, Starodub A, O’Neil B, et al. A phase I/II, first-in-human study of VLS-1488, an oral KIF18A inhibitor, in patients with advanced cancer. JCO 42, TPS3181-TPS3181(2024). doi:10.1200/JCO.2024.42.16_suppl.TPS3181