Chromosomal Instability, Fallopian Tube Cancer, High Grade Serous Adenocarcinoma of Ovary, Primary Peritoneal Carcinoma
Conditions
Keywords
KIF18A Inhibitor
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.
Interventions
DRUGSovilnesib
Sovilnesib tablets will be given orally.
Sponsors
Volastra Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 | Up to 24 months |
| 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 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Duration of Response (DOR) as assessed by RECIST version 1.1 | Up to 24 months |
Countries
United States
Outcome results
None listed