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

Volastra Therapeutics

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Uterine Serous Carcinoma; Endometrium Cancer; Ovarian Carcinosarcoma; High Grade Serous Adenocarcinoma of Ovary; Uterine Carcinosarcoma; Squamous Non-small-cell Lung Cancer; Advanced Solid Tumor; Chromosomal Instability; Triple Negative Breast Cancer; Head and Neck Squamous Cell Carcinoma

Treatments: Drug: VLS-1488

Study type: Interventional

Funder types: Industry

Identifiers

NCT05902988

VLS-1488-2201

Details and patient eligibility

About

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.

Full 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.

Enrollment: 200 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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200 participants in 4 patient groups

Dose Escalation: Dose Escalation Cohorts

Experimental group

Description:

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.

Treatment:

Drug: VLS-1488

Dose Escalation: Backfill Cohorts

Experimental group

Description:

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.

Treatment:

Drug: VLS-1488

Dose Expansion: Exploration Cohorts

Experimental group

Description:

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.

Treatment:

Drug: VLS-1488

Dose Expansion: Development Cohorts

Experimental group

Description:

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.

Treatment:

Drug: VLS-1488