A Study of Sovilnesib in Subjects With Ovarian Cancer

A Phase 1b Dose Optimization Study of Sovilnesib (an Oral KIF18A Inhibitor) in Subjects With Advanced High Grade Serous Ovarian Cancer

This is a randomized, phase 1b study to assess the safety, tolerability, pharmacokinetics (PK), and efficacy of sovilnesib at different dose levels to establish the Recommended Phase 2 Dose (RP2D) of sovilnesib in subjects with high grade serous ovarian cancer (HGSOC).

Study Overview

• Status: Active, not recruiting
• Conditions: Fallopian Tube Cancer; Primary Peritoneal Carcinoma; High Grade Serous Adenocarcinoma of Ovary; Chromosomal Instability
• Intervention / Treatment: Drug: Sovilnesib

Detailed Description

This is a randomized, phase 1b dose optimization study of sovilnesib in subjects with platinum-resistant HGSOC. The focus of the proposed clinical study is to establish the RP2D of sovilnesib in HGSOC.

An adaptive multi-cohort design will be used to assess the safety, tolerability, PK, and efficacy of multiple dose levels in parallel to establish the RP2D of sovilnesib. The study will be conducted in 2 parts.

Part 1: 10 subjects will be randomized to each of the open dose levels to generate preliminary PK, pharmacodynamic (PD), safety, tolerability and efficacy data. Early stopping rules for safety based on a Bayesian Toxicity Monitoring Design will be applied.

Part 2: Based on review of the data from Part 1, 20-30 additional subjects will be randomized to 2 or more dose levels examined in Part 1. At the end of Part 2, PK, PD, safety, tolerability and efficacy data will be used to determine the RP2D. Early stopping rules for safety based on a Bayesian Toxicity Monitoring Design and for futility based on a Bayesian Efficacy Monitoring via Predictive Probability Design will be applied.

Sovilnesib will be given orally in 28-day cycles at selected dose levels of interest. Dosing will continue until disease progression, unacceptable toxicity, withdrawal of consent, or other stopping criteria are met.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • The University of Alabama at Birmingham
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Los Angeles, California, United States, 90095
      • UCLA
    • Newport Beach, California, United States, 92663
      • Hoag Memorial Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30912
      • Georgia Cancer Center Augusta University
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Corewell Health
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Comprehensive Cancer Center
    • New York, New York, United States, 10128
      • Icahn School of Medicine at Mount Sinai
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73117
      • OU Health Stephenson Cancer Center
  • South Carolina
    • Charleston, South Carolina, United States, 29020
      • MUSC Hollings Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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
• High Grade Serous Ovarian Cancer, Fallopian Tube or Primary Peritoneal Cancer - histologically or cytologically confirmed; metastatic or unresectable; platinum resistant (defined as recurrence within 6 months of platinum containing therapy) or platinum refractory; prior bevacizumab treatment, or ineligible or intolerant to bevacizumab, or did not receive bevacizumab based on Investigator judgement; if germline and/or somatic BRCA1/2 mutation, previously treated with PARP-inhibitor or ineligible or intolerant.

Key Exclusion Criteria:

• MSI-H, dMMR, POLE gene hotspot mutated, or known hypermutator phenotype
• Endometrioid, clear cell, mucinous, sarcomatoid, low-grade/borderline ovarian tumor or mixed tumors containing any of the above histologies
• Previously received KIF18A inhibitor
• Current CNS metastases or leptomeningeal disease
• Cardiac parameters: MI or stroke ≤ 6 months, unstable angina/PE/DVT/CABG ≤ 6 months, NYHA Class ≥ II, LVEF < 50%
• Any gastrointestinal condition (e.g. malabsorption syndrome, surgical anastomosis, short bowel syndrome) that might affect the absorption of oral medications including the study drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Level 1; Subjects will receive sovilnesib once daily at Dose Level 1 in 28-day cycles.	Drug: Sovilnesib; Sovilnesib tablets will be given orally.
Experimental: Dose Level 2; Subjects will receive sovilnesib once daily at Dose Level 2 in 28-day cycles.	Drug: Sovilnesib; Sovilnesib tablets will be given orally.
Experimental: Dose Level 3; Subjects will receive sovilnesib once daily at Dose Level 3 in 28-day cycles.	Drug: Sovilnesib; Sovilnesib tablets will be given orally.
Experimental: Dose Level 4; Subjects will receive sovilnesib once daily at Dose Level 4 in 28-day cycles.	Drug: Sovilnesib; Sovilnesib tablets will be given orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determination of the Recommended Phase 2 Dose (RP2D) of Sovilnesib	Up to 24 months
Frequency and duration 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 24 months
Frequency and duration of Treatment-related Adverse Events (AEs) graded per NCI-CTCAE version 5.0	Up to 24 months
Frequency and duration of Treatment-Emergent AEs (TEAEs) graded per NCI-CTCAE version 5.0	Up to 24 months
Frequency of Dose Interruptions and Permanent Treatment Discontinuations	Up to 24 months
Objective Response Rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of Response (DOR) as assessed by RECIST version 1.1	Up to 24 months
Disease Control Rate (DCR) as assessed by RECIST version 1.1	Up to 24 months
Progression Free Survival (PFS) as assessed by RECIST version 1.1	Up to 24 months
Evaluation of CA-125 response by Gynecologic Cancer InterGroup (GCIG) criteria	Up to 24 months
Plasma level of Sovilnesib	Up to 24 months

Collaborators and Investigators

• Sponsor: Volastra Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2024
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: October 10, 2023
• First Submitted That Met QC Criteria: October 10, 2023
• First Posted (Actual): October 16, 2023

Study Record Updates

• Last Update Posted (Estimated): October 20, 2025
• Last Update Submitted That Met QC Criteria: October 15, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: KIF18A Inhibitor
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Female; Adnexal Diseases; Genital Neoplasms, Female; Fallopian Tube Diseases; Chromosome Aberrations; Genomic Instability; Pathological Conditions, Signs and Symptoms; Fallopian Tube Neoplasms; Chromosomal Instability
• Other Study ID Numbers: SOVI-2302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No