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

NCT05251714 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: TWT-203
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 4

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.

Conditions

Advanced Solid Tumor; Breast Cancer

Keywords

advanced solid tumors; advanced breast cancer; CFI-402257; 2257; fulvestrant; TWT-203; TWT203; UHN; University Health Network; Treadwell; Treadwell Therapeutics; endocrine therapy; TTK; TTK inhibitor

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• Assessment of objective response rates

  48 months

• Assessment of objective response rates of the combination

  48 months

• Assessment of the pharmacokinetic profile of CFI-402257 through AUC

  48 months

• Assessment of the pharmacokinetic profile of CFI-402257 in combination with fulvestrant through AUC

  48 months

• To evaluate the effect of CFI-402257 treatment on changes in variant allele function

  48 months

Study Arms (2)

Part A: Monotherapy Escalation and Expansion

EXPERIMENTAL

Dose selection and expansion of CFI-402257

Drug: CFI-402257

Part B: Combination Escalation and Expansion

EXPERIMENTAL

Dose selection and expansion of CFI-402257 with Fulvestrant

Drug: CFI-402257; Drug: Fulvestrant

Interventions

CFI-402257 DRUG

Oral once daily in 28 day cycles

Also known as: 2257, 402257

Part A: Monotherapy Escalation and Expansion; Part B: Combination Escalation and Expansion

Fulvestrant DRUG

500 mg given by IM injection on Day 1 and Day 15 of Cycle 1 and Day 1 of each subsequent cycle

Also known as: Faslodex

Part B: Combination Escalation and Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Have histological or cytological proof of advanced cancer that has progressed on at least 1 prior line of systemic therapy
• Breast cancer patients positive for estrogen receptor and/or progesterone receptor and negative for HER2
• Must have previously received a CDK4/6 inhibitor
• No limit on lines of endocrine therapy
• Must have received no more than 1 line of cytotoxic chemotherapy
• Have measurable disease as per RECIST 1.1 guidelines.
• Breast cancer patients positive for estrogen receptor and/or progesterone receptor and negative for HER2
• Must have previously received a CDK4/6 inhibitor
• Must have previously received no more than 1 line of endocrine therapy
• Must have received no more than 1 line of cytotoxic chemotherapy
• Have measurable disease as per RECIST 1.1 guidelines.

You may not qualify if:

• Are pregnant or nursing.
• 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.
• Received growth factors within 14 days prior to initiation of dosing of CFI-402257 or who will require ongoing treatment with growth factors
• Have active, acute, or clinically significant chronic infections.
• 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.
• Have had major surgery within 21 days of starting therapy.
• Primary central nervous system malignancies or known central nervous system metastasis.
• Being treated with full dose warfarin.
• Coagulopathy or any history of coagulopathy within the past 6 months, including history of deep vein thrombosis or pulmonary embolism.
• Patients must avoid the use of strong CYP3A4 inducers and inhibitors. CYP3A sensitive substrates, PgP, BCRP inhibitors
• Have had prior treatment with a TTK/MPS1 inhibitor.

Sponsors & Collaborators

• Treadwell Therapeutics, Inc: lead

Study Sites (4)

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

START San Antonio

San Antonio, Texas, 78229, United States

Location

START - Mountain Region

West Valley City, Utah, 84119, United States

Location

Virginia Cancer Specialist

Fairfax, Virginia, 22031, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

CFI-402257; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• R Wesolowski

  The Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation and expansion for monotherapy and combination arms with fulvestrant

Study Record Dates

• First Submitted: February 7, 2022
• First Posted: February 23, 2022
• Study Start: May 27, 2022
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: May 18, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)