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

Phase 1

Active, not recruiting

• Conditions: Advanced Solid Tumor; Breast Cancer
• Interventions: Drug: CFI-402257; Drug: Fulvestrant

• Registration Number: NCT05251714
• Lead Sponsor: Treadwell Therapeutics, Inc

Brief Summary

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.

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 Timeline

• Study First Submitted: 2022-02-07
• Study First Submitted QC: 2022-02-11
• Study First Posted: 2022-02-23
• Study Start: 2022-05-27
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-16
• Last Update Posted: 2025-05-18
• Primary Completion: 2026-08
• Study Completion: 2026-08

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 44

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part A: Monotherapy Escalation and Expansion	CFI-402257	Dose selection and expansion of CFI-402257
Part B: Combination Escalation and Expansion	CFI-402257	Dose selection and expansion of CFI-402257 with Fulvestrant
Part B: Combination Escalation and Expansion	Fulvestrant	Dose selection and expansion of CFI-402257 with Fulvestrant

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (4)

The Ohio State University Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States

START San Antonio; 🇺🇸 San Antonio, Texas, United States

START - Mountain Region; 🇺🇸 West Valley City, Utah, United States

Virginia Cancer Specialist; 🇺🇸 Fairfax, Virginia, United States