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

Advanced Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05902988
• Other study ID #: VLS-1488-2201
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 18, 2023
• Est. completion date: June 2026

Study information

• Verified date: March 2024
• Source: Volastra Therapeutics, Inc.
• Contact: Volastra Therapeutics, Inc.
• Phone: (646) 344-1248
• Email: clinicaltrials[@]volastratx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: June 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Advanced Solid Tumor
• Carcinoma
• Carcinoma, Squamous Cell
• Carcinoma, Transitional Cell
• Carcinosarcoma
• Chromosomal Instability
• Colorectal Adenocarcinoma
• Endometrial Neoplasms
• Endometrium Cancer
• Esophageal Adenocarcinoma
• Esophageal Squamous Cell Carcinoma
• Gastric Adenocarcinoma
• Gastroesophageal Junction Adenocarcinoma
• Head and Neck Squamous Cell Carcinoma
• Mixed Tumor, Mullerian
• Ovarian Carcinosarcoma
• Squamous Cell Carcinoma of Head and Neck
• Squamous Non-small-cell Lung Cancer
• Transitional Cell Carcinoma of Bladder
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms
• Urinary Bladder Neoplasms
• Uterine Carcinosarcoma
• Uterine Serous Carcinoma

Intervention

Drug:
• VLS-1488
VLS-1488 tablets will be given orally.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	The Christ Hospital	Cincinnati	Ohio
United States	START Midwest	Grand Rapids	Michigan
United States	M.D. Anderson Cancer Center	Houston	Texas
United States	Community Health Network	Indianapolis	Indiana
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Women & Infants Hospital	Providence	Rhode Island

Sponsors (1)

Lead Sponsor	Collaborator
Volastra Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Escalation: Incidence of Dose Limiting Toxicities (DLTs) in DLT-evaluable subjects		Up to 12 months
Primary	Dose Escalation: Determination of the MTD of VLS-1488		Up to 12 months
Primary	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		Up to 12 months
Primary	Dose Escalation: Frequency of Treatment-related Adverse Events (AEs) graded per NCI-CTCAE version 5.0		Up to 12 months
Primary	Dose Escalation: Frequency of Treatment-Emergent AEs (TEAEs) graded per NCI-CTCAE version 5.0		Up to 12 months
Primary	Dose Escalation: Frequency of Dose Interruptions and Permanent Treatment Discontinuations		Up to 12 months
Primary	Dose Expansion: Frequency of Trigger Events (TEs)		Up to 18 months
Primary	Dose Expansion: Objective Response Rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1		Up to 18 months
Secondary	Dose Escalation: ORR as assessed by RECIST version 1.1		Up to 12 months
Secondary	Dose Expansion: Frequency of SAEs graded according to NCI-CTCAE version 5.0		Up to 18 months
Secondary	Dose Expansion: Frequency of Treatment-related AEs graded according to NCI-CTCAE version 5.0		Up to 18 months
Secondary	Dose Expansion: Frequency of TEAEs graded according to NCI-CTCAE version 5.0		Up to 18 months
Secondary	Dose Expansion: Frequency of Dose Interruptions and Permanent Treatment Discontinuations		Up to 18 months
Secondary	Dose Expansion: Area Under the Plasma Concentration-Time Curve (AUC) of Midazolam and its metabolite 1'-hydroxymidazolam		Up to 18 months
Secondary	Dose Expansion: Maximum Plasma Concentration (Cmax) of Midazolam and its metabolite 1'-hydroxymidazolam		Up to 18 months
Secondary	Dose Expansion: Evaluation of CA-125 response by Gynecologic Cancer InterGroup (GCIG) criteria (High Grade Serous Ovarian Cancer only)		Up to 18 months
Secondary	Dose Escalation & Dose Expansion: Duration of Response (DOR) as assessed by RECIST version 1.1		Up to 32 months
Secondary	Dose Escalation & Dose Expansion: Disease Control Rate (DCR) as assessed by RECIST version 1.1		Up to 32 months
Secondary	Dose Escalation & Dose Expansion: Progression Free Survival (PFS) as assessed by RECIST version 1.1		Up to 32 months
Secondary	Dose Escalation & Dose Expansion: Cmax of VLS-1488		Up to 32 months
Secondary	Dose Escalation & Dose Expansion: AUC of VLS-1488		Up to 32 months
Secondary	Dose Escalation & Dose Expansion: Trough Concentration (Ctrough) of VLS-1488		Up to 32 months
Secondary	Dose Escalation & Dose Expansion: Time to Maximum Plasma Concentration (Tmax) of VLS-1488		Up to 32 months
Secondary	Dose Escalation & Dose Expansion: Ratio of Total Cholesterol to 4ß-hydroxycholesterol in plasma		Up to 32 months
Secondary	Dose Escalation & Dose Expansion: Increase in the number of Phospho-Histone 3 positive tumor cells		Up to 32 months
Secondary	Dose Escalation & Dose Expansion: Frequency of Micronucleated Reticulocytes in blood		Up to 32 months
Secondary	Dose Escalation & Dose Expansion: Increase in Micronuclei in Circulating Tumor Cells		Up to 32 months