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

Phase 2RecruitingNCT05902988

Volastra Therapeutics, Inc.200 enrolled

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.

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

200

Conditions

Advanced Solid Tumor High Grade Serous Adenocarcinoma of Ovary

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (14)

University of Southern California

Los Angeles, California, United States

RECRUITING

Hoag Memorial Hospital

Newport Beach, California, United States

RECRUITING

University of Colorado Cancer Center

Aurora, Colorado, United States

RECRUITING

Yale Cancer Center

New Haven, Connecticut, United States

RECRUITING

Kellogg Cancer Center

Evanston, Illinois, United States

RECRUITING

Community Health Network

Indianapolis, Indiana, United States

RECRUITING

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, United States

RECRUITING

START Midwest

Grand Rapids, Michigan, United States

ACTIVE_NOT_RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

RECRUITING

...and 4 more locations

Outcomes

Primary Outcomes

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 Outcomes

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

Dose Escalation & Dose Expansion: AUC of VLS-1488

Time frame: Up to 32 months

Dose Escalation & Dose Expansion: Trough Concentration (Ctrough) of VLS-1488

Time frame: Up to 32 months

Dose Escalation & Dose Expansion: Time to Maximum Plasma Concentration (Tmax) of VLS-1488

Time frame: Up to 32 months

Dose Escalation & Dose Expansion: Ratio of Total Cholesterol to 4β-hydroxycholesterol in plasma

Time frame: 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

Dose Escalation & Dose Expansion: Frequency of Micronucleated Reticulocytes in blood

Time frame: Up to 32 months

Dose Escalation & Dose Expansion: Increase in Micronuclei in Circulating Tumor Cells

Time frame: Up to 32 months

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

Overview

Conditions

Interventions

Eligibility

Locations (14)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts