Advanced Solid Tumor Clinical Trial
Official title:
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.
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 |
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 | Yale Cancer Center | New Haven | Connecticut |
United States | Memorial Sloan Kettering Cancer Center | New York | New York |
United States | Women & Infants Hospital | Providence | Rhode Island |
Lead Sponsor | Collaborator |
---|---|
Volastra Therapeutics, Inc. |
United States,
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 |
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