FDA Grants Fast Track Status to VLS-1488 for Platinum-Resistant High-Grade Serous Ovarian Cancer

The FDA has granted fast track designation to VLS-1488 for use as a potential therapeutic option in patients with platinum-resistant high-grade serous ovarian cancer (HGSOC), according to an announcement from drug developer Volastra Therapeutics.¹

The safety, tolerability, and preliminary efficacy of the KIF18A inhibitor is being explored in patients with advanced cancers, including those with HGSOC, as part of a first-in-human phase 1/2 study (NCT05902988).²

“Platinum-resistant high-grade serous ovarian cancer is marked by poor prognosis, highlighting the urgent need for new therapies for this devastating disease,” Scott Drutman, MD, PhD, head of Research & Development and chief medical officer at Volastra, stated in a press release.¹ “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.”

The early-phase study is enrolling patients who are at least 18 years of age, have an ECOG performance status of 0 or 1, at least 1 site of measurable disease by RECIST 1.1 criteria, and who are able to receive oral medication.²

The dose-escalation portion of the research will include patients with HGSOC, squamous non–small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), gastric adenocarcinoma without Epstein–Barr virus (EBV) positivity, colorectal cancer (CRC), esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma, gastroesophageal junction cancer, transitional cell bladder cancer, ovarian carcinosarcoma, copy number (CN)–high endometrial or uterine cancer, or head and neck squamous cell carcinomas (HNSCC; excluding nasopharynx, sinonasal, or lip) who do not have available therapeutic options that provide clinically meaningful benefits.

The key objective of this phase is to examine the safety and tolerability of VLS-1488 at several dose levels utilizing a series of dose escalation and backfill cohorts. Specifically, investigators will determine a maximum tolerated dose and identify which dose levels to further explore in the expansion phase.

The expansion phase will include patients with HGSOC, squamous NSCLC, TNBC, gastric adenocarcinoma without EBV positivity, CRC, ESCC, esophageal adenocarcinoma, CN-high endometrial or uterine cancer, and HNSCC (excluding nasopharynx, sinonasal, or lip) who previously received several lines of standard-of-care therapy specified in the trial protocol. Here, investigators will further evaluate the safety and tolerability of the agent, as well as drug-drug interaction risk, food effect, and preliminary efficacy.

The oral investigative agent will be administered as part of 28-day cycles and treatment will continue until progressive disease, intolerable toxicity, withdrawn consent, or other discontinuation criteria are met.

A study is estimated to enroll approximately 120 patients, and has a primary completion estimate of December 2025.

References

1. Volastra Therapeutics granted FDA fast track designation for novel KIF18A inhibitor in ovarian cancer. News release. Volastra Therapeutics. October 2, 2024. Accessed October 2, 2024. https://www.volastratx.com/volastra-therapeutics-granted-fda-fast-track-designation-for-novel-kif18a-inhibitor-in-ovarian-cancer/
2. A phase I/II study of VLS-1488 in subjects with advanced cancer. ClinicalTrials.gov. Updated September 19, 2024. Accessed October 2, 2024. https://clinicaltrials.gov/study/NCT05902988