A Study of Sovilnesib in Subjects With Ovarian Cancer

Fallopian Tube Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06084416
• Other study ID #: SOVI-2302
• Status: Recruiting
• Phase: Phase 1
• Start date: April 4, 2024
• Est. completion date: July 2025

Study information

• Verified date: April 2024
• Source: Volastra Therapeutics, Inc.
• Contact: Volastra Therapeutics, Inc.
• Phone: (646) 344-1248
• Email: clinicaltrials[@]volastratx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: July 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

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
• 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

Related Conditions & MeSH terms

• Chromosomal Instability
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Primary Peritoneal Carcinoma

Intervention

Drug:
• Sovilnesib
Sovilnesib tablets will be given orally.

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Volastra Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of the Recommended Phase 2 Dose (RP2D) of Sovilnesib		Up to 24 months
Primary	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
Primary	Frequency and duration of Treatment-related Adverse Events (AEs) graded per NCI-CTCAE version 5.0		Up to 24 months
Primary	Frequency and duration of Treatment-Emergent AEs (TEAEs) graded per NCI-CTCAE version 5.0		Up to 24 months
Primary	Frequency of Dose Interruptions and Permanent Treatment Discontinuations		Up to 24 months
Primary	Objective Response Rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1		Up to 24 months
Secondary	Duration of Response (DOR) as assessed by RECIST version 1.1		Up to 24 months
Secondary	Disease Control Rate (DCR) as assessed by RECIST version 1.1		Up to 24 months
Secondary	Progression Free Survival (PFS) as assessed by RECIST version 1.1		Up to 24 months
Secondary	Evaluation of CA-125 response by Gynecologic Cancer InterGroup (GCIG) criteria		Up to 24 months
Secondary	Plasma level of Sovilnesib		Up to 24 months