Clinical trial NCT06084416: A Study of Sovilnesib in Subjects with Ovarian Cancer
Official title: A Phase 1b Dose Optimization Study of Sovilnesib (an Oral KIF18A Inhibitor) in Subjects with Advanced High Grade Serous Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: High Grade Serous Adenocarcinoma of Ovary
Fallopian Tube Cancer
Primary Peritoneal Carcinoma
Chromosomal Instability
Keywords: KIF18A Inhibitor
Lead sponsor: Volastra Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2023-10-16
Enrollment: 120
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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
* 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

Primary outcomes:
measure: Determination of the Recommended Phase 2 Dose (RP2D) of Sovilnesib
timeFrame: Up to 24 months
measure: 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
timeFrame: Up to 24 months
measure: Frequency and duration of Treatment-related Adverse Events (AEs) graded per NCI-CTCAE version 5.0
timeFrame: Up to 24 months
measure: Frequency and duration of Treatment-Emergent AEs (TEAEs) graded per NCI-CTCAE version 5.0
timeFrame: Up to 24 months
measure: Frequency of Dose Interruptions and Permanent Treatment Discontinuations
timeFrame: Up to 24 months
measure: Objective Response Rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
timeFrame: Up to 24 months
Secondary outcomes:
measure: Duration of Response (DOR) as assessed by RECIST version 1.1
timeFrame: Up to 24 months
measure: Disease Control Rate (DCR) as assessed by RECIST version 1.1
timeFrame: Up to 24 months
measure: Progression Free Survival (PFS) as assessed by RECIST version 1.1
timeFrame: Up to 24 months
measure: Evaluation of CA-125 response by Gynecologic Cancer InterGroup (GCIG) criteria
timeFrame: Up to 24 months
measure: Plasma level of Sovilnesib
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham
state: Alabama
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital
state: California
city: Atlanta
country: United States
facility: Georgia Cancer Center Augusta University
state: Georgia
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Grand Rapids
country: United States
facility: Corewell Health
state: Michigan
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Oklahoma City
country: United States
facility: OU Health Stephenson Cancer Center
state: Oklahoma
city: Charleston
country: United States
facility: MUSC Hollings Cancer Center
state: South Carolina
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
Study officials:
References: