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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05251714
• Other study ID #: TWT-203
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 27, 2022
• Est. completion date: August 2025

Study information

• Verified date: April 2024
• Source: Treadwell Therapeutics, Inc
• Contact: Treadwell Therapeutics Clinical Trials
• Phone: +1-416-455-7510
• Email: clinicaltrials[@]treadwelltx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 44
• Est. completion date: August 2025
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• CFI-402257
Oral once daily in 28 day cycles
• Fulvestrant
500 mg given by IM injection on Day 1 and Day 15 of Cycle 1 and Day 1 of each subsequent cycle

Locations

Country	Name	City	State
United States	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Virginia Cancer Specialist	Fairfax	Virginia
United States	START San Antonio	San Antonio	Texas
United States	START - Mountain Region	West Valley City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Treadwell Therapeutics, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	Assessment of objective response rates of the combination	Objective response rate will be summarized overall for advanced breast cancer patients	48 months
Secondary	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
Secondary	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
Secondary	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