Clinical trial NCT05251714: CFI-402257, a Potent and Selective TTK Inhibitor, in Solid Tumors and With Fulvestrant in Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
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
Lead sponsor: Treadwell Therapeutics, Inc
Sponsor class: INDUSTRY
First posted: 2022-02-23
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose escalation and expansion for monotherapy and combination arms with fulvestrant
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: To assess the incidence of adverse events of CFI-402257 as a single agent and at the recommended phase 2 dose (RP2D)
timeFrame: 48 months
measure: To assess the incidence of adverse events of CFI-402257 in combination with fulvestrant and at the recommended phase 2 dose (RP2D)
timeFrame: 48 months
Secondary outcomes:
measure: Assessment of objective response rates
timeFrame: 48 months
measure: Assessment of objective response rates of the combination
timeFrame: 48 months
measure: Assessment of the pharmacokinetic profile of CFI-402257 through AUC
timeFrame: 48 months
measure: Assessment of the pharmacokinetic profile of CFI-402257 in combination with fulvestrant through AUC
timeFrame: 48 months
measure: To evaluate the effect of CFI-402257 treatment on changes in variant allele function
timeFrame: 48 months
Other outcomes:
Locations:
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: San Antonio
country: United States
facility: START San Antonio
state: Texas
city: West Valley City
country: United States
facility: START - Mountain Region
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialist
state: Virginia
Study officials:
affiliation: The Ohio State University Comprehensive Cancer Center
name: R Wesolowski
role: PRINCIPAL_INVESTIGATOR
References: