A Study of Sovilnesib in Subjects With Ovarian Cancer
- Conditions
- Chromosomal InstabilityHigh Grade Serous Adenocarcinoma of OvaryPrimary Peritoneal CarcinomaFallopian Tube Cancer
- Interventions
- Registration Number
- NCT06084416
- Lead Sponsor
- Volastra Therapeutics, Inc.
- Brief Summary
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).
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 120
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dose Level 4 Sovilnesib Subjects will receive sovilnesib once daily at Dose Level 4 in 28-day cycles. Dose Level 1 Sovilnesib Subjects will receive sovilnesib once daily at Dose Level 1 in 28-day cycles. Dose Level 2 Sovilnesib Subjects will receive sovilnesib once daily at Dose Level 2 in 28-day cycles. Dose Level 3 Sovilnesib Subjects will receive sovilnesib once daily at Dose Level 3 in 28-day cycles.
- Primary Outcome Measures
Name Time Method Frequency and duration of Treatment-related Adverse Events (AEs) graded per NCI-CTCAE version 5.0 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 Determination of the Recommended Phase 2 Dose (RP2D) of Sovilnesib 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 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
- Secondary Outcome Measures
Name Time Method Evaluation of CA-125 response by Gynecologic Cancer InterGroup (GCIG) criteria Up to 24 months Plasma level of Sovilnesib Up to 24 months 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
Trial Locations
- Locations (13)
The University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
UCLA
🇺🇸Los Angeles, California, United States
Hoag Memorial Hospital
🇺🇸Newport Beach, California, United States
Georgia Cancer Center Augusta University
🇺🇸Atlanta, Georgia, United States
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Corewell Health
🇺🇸Grand Rapids, Michigan, United States
Roswell Park Comprehensive Cancer Center
🇺🇸Buffalo, New York, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
OU Health Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
MUSC Hollings Cancer Center
🇺🇸Charleston, South Carolina, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States