a phase i/ii study of vls-1488 in subjects with advanced cancer

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

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.

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.

Eligibility 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

Keywords: kif18a inhibitor