CFI-402257, a Potent and Selective TTK Inhibitor, in Solid Tumors and With Fulvestrant in Breast Cancer

A Dose-confirming Study of CFI-402257 as a Single Agent in Advanced Solid Tumors and in Combination With Fulvestrant in Patients With ER+/HER2- Advanced Breast Cancer After Disease Progression on Prior CDK4/6 and Endocrine Therapy

The purpose of this study is to test the safety of an investigational drug called CFI-402257 alone in advanced solid tumors and in combination with Fulvestrant in advanced breast cancer patients.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer; Advanced Solid Tumor
• Intervention / Treatment: Drug: CFI-402257; Drug: Fulvestrant

Detailed Description

This study will be evaluating the safety and tolerability of CFI-402257 in subjects with advanced solid tumors and in advanced breast cancer. The study is designed to build on encouraging data from another study and to obtain further safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) data of CFI-402257.

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Comprehensive Cancer Center
  • Texas
    • San Antonio, Texas, United States, 78229
      • START San Antonio
  • Utah
    • West Valley City, Utah, United States, 84119
      • START - Mountain Region
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialist

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria: Part A Escalation

1. Have histological or cytological proof of advanced cancer that has progressed on at least 1 prior line of systemic therapy

Inclusion Criteria: Part A Expansion

1. Breast cancer patients positive for estrogen receptor and/or progesterone receptor and negative for HER2
2. Must have previously received a CDK4/6 inhibitor
3. No limit on lines of endocrine therapy
4. Must have received no more than 1 line of cytotoxic chemotherapy
5. Have measurable disease as per RECIST 1.1 guidelines.

Inclusion Criteria: Part B

1. Breast cancer patients positive for estrogen receptor and/or progesterone receptor and negative for HER2
2. Must have previously received a CDK4/6 inhibitor
3. Must have previously received no more than 1 line of endocrine therapy
4. Must have received no more than 1 line of cytotoxic chemotherapy
5. Have measurable disease as per RECIST 1.1 guidelines.

Exclusion Criteria: All Parts

1. Are pregnant or nursing.
2. Have received chemotherapy, biological therapy, or investigational treatment less than 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to first dose of study drug. Have received radiotherapy less than 2 weeks prior to first dose of study drug.
3. Received growth factors within 14 days prior to initiation of dosing of CFI-402257 or who will require ongoing treatment with growth factors
4. Have active, acute, or clinically significant chronic infections.

5. Have the following cardiovascular conditions

   • Have uncontrolled severe hypertension
   • Have symptomatic congestive heart failure
   • Have active angina pectoris or recent myocardial infarction
   • Have chronic atrial fibrillation or QTc of greater than 470 msec.
6. Have had major surgery within 21 days of starting therapy.
7. Primary central nervous system malignancies or known central nervous system metastasis.
8. Being treated with full dose warfarin.
9. Coagulopathy or any history of coagulopathy within the past 6 months, including history of deep vein thrombosis or pulmonary embolism.
10. Patients must avoid the use of strong CYP3A4 inducers and inhibitors. CYP3A sensitive substrates, PgP, BCRP inhibitors
11. Have had prior treatment with a TTK/MPS1 inhibitor.
12. Part B only: Known bleeding disorder which would prohibit administration of fulvestrant.
13. Part B only: Concomitant active malignancy other than ER+/HER2- advanced breast cancer.
14. Part A only: Concomitant active malignancy other than primary malignancy
15. Part B only: Had prior treatment with fulvestrant or agents with similar MoA

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Monotherapy Escalation and Expansion; Dose selection and expansion of CFI-402257	Drug: CFI-402257; Oral once daily in 28 day cycles; Other Names: 2257; 402257
Experimental: Part B: Combination Escalation and Expansion; Dose selection and expansion of CFI-402257 with Fulvestrant	Drug: CFI-402257; Oral once daily in 28 day cycles; Other Names: 2257; 402257; Drug: Fulvestrant; 500 mg given by IM injection on Day 1 and Day 15 of Cycle 1 and Day 1 of each subsequent cycle; Other Names: Faslodex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the incidence of adverse events of CFI-402257 as a single agent and at the recommended phase 2 dose (RP2D)	The number of subjects who experience an adverse event that was possibly related to study drug as assessed by CTCAE v 5.0.	48 months
To assess the incidence of adverse events of CFI-402257 in combination with fulvestrant and at the recommended phase 2 dose (RP2D)	The number of subjects who experience an adverse event that was possibly related to study drug as assessed by CTCAE v 5.0.	48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of objective response rates	Objective response rate will be summarized by dose cohort and overall using the percent of patients in each tumor response category.	48 months
Assessment of objective response rates of the combination	Objective response rate will be summarized overall for advanced breast cancer patients	48 months
Assessment of the pharmacokinetic profile of CFI-402257 through AUC	Area under the plasma concentration (AUC) versus time curve from time 0 to time of least measurable concentration tabulated by dose group.	48 months
Assessment of the pharmacokinetic profile of CFI-402257 in combination with fulvestrant through AUC	Area under the plasma concentration (AUC) versus time curve from time 0 to time of least measurable concentration tabulated by dose group.	48 months
To evaluate the effect of CFI-402257 treatment on changes in variant allele function	Changes in variant allele function will be measured by looking at circulating tumor deoxyribonucleic acid compared to baseline	48 months

Collaborators and Investigators

• Sponsor: Treadwell Therapeutics, Inc
• Investigators: Principal Investigator: R Wesolowski, The Ohio State University Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2022
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: February 7, 2022
• First Submitted That Met QC Criteria: February 11, 2022
• First Posted (Actual): February 23, 2022

Study Record Updates

• Last Update Posted (Actual): May 18, 2025
• Last Update Submitted That Met QC Criteria: May 16, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: advanced solid tumors; advanced breast cancer; TTK; fulvestrant; endocrine therapy; UHN; University Health Network; Treadwell Therapeutics; CFI-402257; 2257; TWT-203; TWT203; Treadwell; TTK inhibitor
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Estrogen Receptor Antagonists; Estrogen Antagonists; Fulvestrant
• Other Study ID Numbers: TWT-203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: It is too early to determine whether we will make IPD available - we do not yet have a process written on this. Field will be updated once our policy / process is written.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No