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Recruiting NCT05902988

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

Phase I / Phase II Interventional Advanced Solid Tumor High Grade Serous Adenocarcinoma of Ovary Squamous Non-small-cell Lung Cancer Triple Negative Breast Cancer

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: VLS-1488.
Who it may be relevant to
Registry conditions: Advanced Solid Tumor, High Grade Serous Adenocarcinoma of Ovary, Squamous Non-small-cell Lung Cancer, Triple Negative Breast Cancer. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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

Overview

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.

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.

Interventions

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

Primary outcome measures

  • Dose Escalation: Incidence of Dose Limiting Toxicities (DLTs) in DLT-evaluable subjects [Time frame: Up to 12 months]
  • Dose Escalation: Determination of the MTD of VLS-1488 [Time frame: 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]
  • Dose Escalation: Frequency of Treatment-related Adverse Events (AEs) graded per NCI-CTCAE version 5.0 [Time frame: 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]
  • Dose Escalation: Frequency of Dose Interruptions and Permanent Treatment Discontinuations [Time frame: Up to 12 months]
  • Dose Expansion: Frequency of Trigger Events (TEs) [Time frame: 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]
Secondary outcome measures (12)
  • Dose Escalation: ORR as assessed by RECIST version 1.1 [Time frame: Up to 12 months]
  • Dose Expansion: Frequency of SAEs graded according to NCI-CTCAE version 5.0 [Time frame: 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]
  • Dose Expansion: Frequency of TEAEs graded according to NCI-CTCAE version 5.0 [Time frame: Up to 18 months]
  • Dose Expansion: Frequency of Dose Interruptions and Permanent Treatment Discontinuations [Time frame: 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]
  • Dose Expansion: Maximum Plasma Concentration (Cmax) of Midazolam and its metabolite 1'-hydroxymidazolam [Time frame: 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]
  • Dose Escalation & Dose Expansion: Duration of Response (DOR) as assessed by RECIST version 1.1 [Time frame: 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]
  • Dose Escalation & Dose Expansion: Progression Free Survival (PFS) as assessed by RECIST version 1.1 [Time frame: Up to 32 months]
  • Dose Escalation & Dose Expansion: Cmax of VLS-1488 [Time frame: Up to 32 months]

Eligibility criteria

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

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Non-randomized
Model
Sequential
Masking
Open label
Primary purpose
Treatment

Study locations

United States · 14 centers
  • University of Southern California — Los Angeles
  • Hoag Memorial Hospital — Newport Beach
  • University of Colorado Cancer Center — Aurora
  • Yale Cancer Center — New Haven
  • Kellogg Cancer Center — Evanston
  • Community Health Network — Indianapolis
  • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center — Baltimore
  • University of Michigan — Ann Arbor
  • … and 6 more centers

Identifiers

NCT: NCT05902988 · VLS-1488-2201

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗