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

INTRODUCTION

  • Org Study ID: VLS-1488-2201
  • Secondary ID: N/A
  • NCT ID: NCT05902988
  • Sponsor: Volastra Therapeutics, Inc.

BRIEF 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.

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.

  • Overall Status
    Recruiting
  • Start Date
    October 18, 2023
  • Phase
    PHASE1, PHASE2
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure:

Primary Outcome 1 - Timeframe: N/A

CONDITION

  • 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

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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: N/A

Role: N/A

Affiliation: N/A

Overall Contact

Name: Volastra Therapeutics, Inc.

Phone: (646) 344-1248

Email: clinicaltrials@volastratx.com

LOCATION

Facility Status Contact
Facility: Community Health Network
Indianapolis, Indiana 46256
United States
Status: Recruiting Contact: Contact
Megan Haas
mhaas2@ecommunity.com

Facility: Memorial Sloan Kettering Cancer Center
New York, New York 10065
United States
Status: Recruiting Contact: Contact
Claire Friedman, MD
646-888-4593
friedmac@mskcc.org

Facility: The Christ Hospital
Cincinnati, Ohio 45219
United States
Status: Recruiting Contact: Contact
Abby Reed, RN
513-585-1140
abby.reed@thechristhospital.com

Facility: Women & Infants Hospital
Providence, Rhode Island 02905
United States
Status: Recruiting Contact: Contact
Emma Locke
401-430-8181
oncologyresearch@wihri.org

Facility: M.D. Anderson Cancer Center
Houston, Texas 77030
United States
Status: Recruiting Contact: Contact
Ecaterina Dumbravca, MD
713-792-3934
eeileana@mdanderson.org