A Phase I/II Study of VLS-1488 in Subjects With Advanced Cancer

October 31, 2025 updated by: Volastra Therapeutics, Inc.

A Phase I/II Study of VLS-1488 (an Oral KIF18A Inhibitor) in Subjects With Advanced Cancer

This is a first-in-human phase I/II study to examine the safety, tolerability and preliminary efficacy of VLS-1488 in subjects with advanced cancers.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This a first-in-human phase I/II study designed to assess the safety, tolerability and preliminary efficacy of VLS-1488 monotherapy and consists of two parts: Dose Escalation and Dose Expansion.

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 identify the Maximum Tolerated Dose (MTD) and to select dose levels for Dose Expansion. The criteria for dose (de-)escalation will be based on a Bayesian Optimal Interval (BOIN) design.

Dose Expansion will examine the safety, tolerability, Drug Drug Interaction (DDI) risk, Food Effect (FE) and preliminary efficacy of VLS-1488 in different tumor types and/or dose levels of interest through various expansion cohorts.

VLS-1488 will be given orally in 28-day cycles. Dosing will be continued until disease progression, unacceptable toxicity, withdrawal of consent, or other stopping criteria are met.

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
    • Colorado
      • Aurora, Colorado, United States, 80045
    • Connecticut
      • New Haven, Connecticut, United States, 06511
        • Recruiting
        • Yale Cancer Center
        • Contact:
    • Illinois
      • Evanston, Illinois, United States, 60201
        • Recruiting
        • Kellogg Cancer Center
        • Contact:
    • Indiana
      • Indianapolis, Indiana, United States, 46256
    • Maryland
      • Baltimore, Maryland, United States, 21224
        • Recruiting
        • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
        • Contact:
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
      • Grand Rapids, Michigan, United States, 49546
        • Active, not recruiting
        • START Midwest
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
    • Ohio
      • Cincinnati, Ohio, United States, 45219
    • Rhode Island
      • Providence, Rhode Island, United States, 02905
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • M.D. Anderson Cancer Center
        • Contact:
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Froedtert & the Medical College of Wisconsin
        • Contact:
          • Clinical Trials Office
          • Phone Number: 414-805-8900
          • Email: cccto@mcw.edu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  • All Parts: Age ≥ 18 years, ECOG Performance Status ≤ 1, at least 1 site of measurable disease evaluable by CT scan or MRI per RECIST 1.1, able to take oral medication without alteration
  • Dose Escalation: No available therapeutic options to provide clinically meaningful benefits in the following tumor types: High Grade Serous Ovarian Cancer, Squamous Non -Small Cell Lung Cancer, Triple Negative Breast Cancer, Gastric Adenocarcinoma (not EBV+), Colorectal, Esophageal Squamous Cell Carcinoma, Esophageal Adenocarcinoma, Gastroesophageal Junction, Bladder (transitional cell), Head and Neck Squamous Cell Carcinomas (not nasopharynx, sinonasal or lip), Ovarian Carcinosarcoma, CN-high Endometrial/Uterine
  • Dose Expansion: Must have been previously treated with several lines of standard of care treatment specified in the protocol in the following tumor types: High Grade Serous Ovarian Cancer, Squamous Non-Small Cell Lung Cancer, Triple Negative Breast Cancer, Gastric Adenocarcinoma (not EBV+), Colorectal, Esophageal Squamous Cell Carcinoma, Esophageal Adenocarcinoma, Head and Neck Squamous Cell Carcinomas (not nasopharynx, sinonasal or lip), CN-high Endometrial/Uterine

Key Exclusion Criteria:

  • MSI-H, dMMR, POLE gene hotspot mutated, or known hypermutator phenotype
  • Previously received KIF18A inhibitor
  • Current CNS metastases or leptomeningeal disease
  • Cardiac parameters: MI or stroke ≤ 1 year, unstable angina/PE/DVT/CABG ≤ 6 months, NYHA Class ≥ II, LVEF < 50%
  • Inability to comply with concomitant medication restrictions with respect to strong inhibitors and inducers of CYP3A, and clinical inhibitors of MDR1 (P-gp) and BCRP
  • Any clinically significant ascites or pleural effusions at time of enrollment, or any therapeutic paracentesis or thoracentesis within 28 days of planned first dose of study drug
  • Bowel obstruction or GI perforation within 6 months of planned first dose of study drug

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose Escalation: Dose Escalation Cohorts
Subjects will be enrolled at various doses and/or schedules of VLS-1488. These Dose Escalation Cohorts will be utilized to identify the MTD and to select dose levels for Dose Expansion.
Drug: VLS-1488
VLS-1488 tablets will be given orally.
Experimental: Dose Escalation: Backfill Cohorts
Additional subjects may be enrolled at any dose level that does not meet de-escalation or elimination rules per the BOIN design. These Backfill Cohorts will be utilized to build additional data to support selection of doses and/or tumor types for further study in Dose Expansion.
Drug: VLS-1488
VLS-1488 tablets will be given orally.
Experimental: Dose Expansion: Exploration Cohorts
Subjects with a selected single tumor type will be randomized 1:1 into Exploration Cohorts at two or more dose levels of interest. A subset of subjects will have additional assessments to examine the potential for VLS-1488 to interact with other drugs and the effect of food on VLS-1488 absorption.
Drug: VLS-1488
VLS-1488 tablets will be given orally.
Experimental: Dose Expansion: Development Cohorts
Subjects with other tumor types will be enrolled at a single dose level of interest. These Development Cohorts will be utilized to examine the preliminary efficacy of VLS-1488 in various tumor types.
Drug: VLS-1488
VLS-1488 tablets will be given orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Dose Escalation: Incidence of Dose Limiting Toxicities (DLTs) in DLT-evaluable subjects
Time Frame: Up to 12 months
Up to 12 months
Dose Escalation: Determination of the MTD of VLS-1488
Time Frame: Up to 12 months
Up to 12 months
Dose Escalation: Frequency of Serious Adverse Events (SAEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0
Time Frame: Up to 12 months
Up to 12 months
Dose Escalation: Frequency of Treatment-related Adverse Events (AEs) graded per NCI-CTCAE version 5.0
Time Frame: Up to 12 months
Up to 12 months
Dose Escalation: Frequency of Treatment-Emergent AEs (TEAEs) graded per NCI-CTCAE version 5.0
Time Frame: Up to 12 months
Up to 12 months
Dose Escalation: Frequency of Dose Interruptions and Permanent Treatment Discontinuations
Time Frame: Up to 12 months
Up to 12 months
Dose Expansion: Frequency of Trigger Events (TEs)
Time Frame: Up to 18 months
Up to 18 months
Dose Expansion: Objective Response Rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time Frame: Up to 18 months
Up to 18 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Dose Escalation: ORR as assessed by RECIST version 1.1
Time Frame: Up to 12 months
Up to 12 months
Dose Expansion: Frequency of SAEs graded according to NCI-CTCAE version 5.0
Time Frame: Up to 18 months
Up to 18 months
Dose Expansion: Frequency of Treatment-related AEs graded according to NCI-CTCAE version 5.0
Time Frame: Up to 18 months
Up to 18 months
Dose Expansion: Frequency of TEAEs graded according to NCI-CTCAE version 5.0
Time Frame: Up to 18 months
Up to 18 months
Dose Expansion: Frequency of Dose Interruptions and Permanent Treatment Discontinuations
Time Frame: Up to 18 months
Up to 18 months
Dose Expansion: Area Under the Plasma Concentration-Time Curve (AUC) of Midazolam and its metabolite 1'-hydroxymidazolam
Time Frame: Up to 18 months
Up to 18 months
Dose Expansion: Maximum Plasma Concentration (Cmax) of Midazolam and its metabolite 1'-hydroxymidazolam
Time Frame: Up to 18 months
Up to 18 months
Dose Expansion: Evaluation of CA-125 response by Gynecologic Cancer InterGroup (GCIG) criteria (High Grade Serous Ovarian Cancer only)
Time Frame: Up to 18 months
Up to 18 months
Dose Escalation & Dose Expansion: Duration of Response (DOR) as assessed by RECIST version 1.1
Time Frame: Up to 32 months
Up to 32 months
Dose Escalation & Dose Expansion: Disease Control Rate (DCR) as assessed by RECIST version 1.1
Time Frame: Up to 32 months
Up to 32 months
Dose Escalation & Dose Expansion: Progression Free Survival (PFS) as assessed by RECIST version 1.1
Time Frame: Up to 32 months
Up to 32 months
Dose Escalation & Dose Expansion: Cmax of VLS-1488
Time Frame: Up to 32 months
Up to 32 months
Dose Escalation & Dose Expansion: AUC of VLS-1488
Time Frame: Up to 32 months
Up to 32 months
Dose Escalation & Dose Expansion: Trough Concentration (Ctrough) of VLS-1488
Time Frame: Up to 32 months
Up to 32 months
Dose Escalation & Dose Expansion: Time to Maximum Plasma Concentration (Tmax) of VLS-1488
Time Frame: Up to 32 months
Up to 32 months
Dose Escalation & Dose Expansion: Ratio of Total Cholesterol to 4β-hydroxycholesterol in plasma
Time Frame: Up to 32 months
Up to 32 months
Dose Escalation & Dose Expansion: Increase in the number of Phospho-Histone 3 positive tumor cells
Time Frame: Up to 32 months
Up to 32 months
Dose Escalation & Dose Expansion: Frequency of Micronucleated Reticulocytes in blood
Time Frame: Up to 32 months
Up to 32 months
Dose Escalation & Dose Expansion: Increase in Micronuclei in Circulating Tumor Cells
Time Frame: Up to 32 months
Up to 32 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Volastra Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 18, 2023

Primary Completion (Estimated)

June 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

May 31, 2023

First Submitted That Met QC Criteria

June 2, 2023

First Posted (Actual)

June 15, 2023

Study Record Updates

Last Update Posted (Estimated)

November 4, 2025

Last Update Submitted That Met QC Criteria

October 31, 2025

Last Verified

October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VLS-1488-2201

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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