CFI-402257 + Fulvestrant for Breast Cancer

Not currently recruiting at 3 trial locations

Overseen By Treadwell Therapeutics Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Treadwell Therapeutics, Inc

Must be taking: CDK4/6 inhibitors

Must not be taking: Warfarin, CYP3A4 inducers

Disqualifiers: Pregnancy, Infections, Cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, CFI-402257, for safety in people with advanced cancer. One part of the trial examines CFI-402257 alone in any advanced cancer, while another part combines it with Fulvestrant (a hormone therapy) to treat certain types of advanced breast cancer. Suitable participants have advanced breast cancer that tests positive for estrogen or progesterone receptors but negative for HER2 and have tried at least one other treatment. The trial aims to determine the best dose and assess how well the treatments work together. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial requires that you avoid using certain medications, specifically strong CYP3A4 inducers and inhibitors, and some other specific drugs. If you are taking these, you may need to stop or adjust them before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that CFI-402257, when used alone, is generally safe in early studies, with most patients not experiencing severe side effects. When combined with Fulvestrant, the safety remained manageable, indicating that side effects were not too harsh for most people.

CFI-402257, whether used alone or with Fulvestrant, has been studied in individuals with advanced cancers. These studies found that the drugs are usually well-tolerated, suggesting that most people did not have serious negative reactions. While current studies suggest the drugs are safe, ongoing trials will provide more information about their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of CFI-402257 with Fulvestrant for breast cancer because it offers a novel approach to treatment. Unlike the standard of care, which often involves hormone therapies like Tamoxifen or Aromatase Inhibitors, CFI-402257 is a unique agent that targets specific cell cycle pathways, potentially inhibiting cancer cell proliferation more effectively. When combined with Fulvestrant, which disrupts estrogen receptor signaling, this duo could provide a more comprehensive attack on cancer cells. This combination aims to enhance treatment efficacy and overcome resistance seen with current therapies.

What evidence suggests that CFI-402257 and Fulvestrant could be effective for advanced breast cancer?

Research has shown that CFI-402257 is a promising treatment for advanced solid tumors. It blocks a protein called TTK, which aids cancer cell growth. In this trial, some participants will receive CFI-402257 alone. Studies have found that this drug can shrink tumors in some patients when used as a monotherapy. Other participants will receive a combination of CFI-402257 with Fulvestrant. This combination has shown early signs of effectiveness and is generally well-tolerated by patients. Fulvestrant already treats certain types of breast cancer, and using it with CFI-402257 might enhance its effectiveness. Overall, early findings suggest that this combination could help treat advanced breast cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

R Wesolowski

Principal Investigator

The Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors or breast cancer that's positive for estrogen/progesterone receptors but negative for HER2. They must have tried certain therapies before, like a CDK4/6 inhibitor and possibly one line of endocrine therapy or chemotherapy. People can't join if they have brain cancer, serious heart conditions, are pregnant/nursing, had recent treatments/surgery, infections, blood clots or coagulopathy.

Inclusion Criteria

You have breast cancer that is positive for estrogen receptor and/or progesterone receptor, but negative for HER2. You have previously taken a CDK4/6 inhibitor and have received no more than one round of chemotherapy. You have measurable disease based on specific guidelines.

My advanced cancer has worsened despite previous treatment.

I have ER+/PR+ HER2- breast cancer, treated with CDK4/6 inhibitors, and limited prior therapy.

Exclusion Criteria

Are pregnant or nursing

I do not have severe uncontrolled high blood pressure, heart failure symptoms, chest pain, recent heart attack, constant irregular heartbeat, or a long QT interval.

I have been treated with a TTK/MPS1 inhibitor before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Monotherapy Escalation and Expansion

Dose selection and expansion of CFI-402257 as a single agent in advanced solid tumors

48 months

Combination Escalation and Expansion

Dose selection and expansion of CFI-402257 in combination with Fulvestrant in advanced breast cancer

48 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CFI-402257
• Fulvestrant

Trial Overview The study tests CFI-402257 alone in various advanced cancers and combined with Fulvestrant specifically in advanced breast cancer patients. It aims to determine the safety of these treatments and how well they work against these cancers.

How Is the Trial Designed?

Group I: Part B: Combination Escalation and Expansion Experimental Treatment 2 Interventions

Dose selection and expansion of CFI-402257 with Fulvestrant

Group II: Part A: Monotherapy Escalation and Expansion Experimental Treatment 1 Intervention

Dose selection and expansion of CFI-402257

Who Is Running the Clinical Trial?

Treadwell Therapeutics, Inc

Lead Sponsor

Trials

4

Recruited

300+

Published Research Related to This Trial

In a study of 402 postmenopausal women with advanced breast cancer receiving fulvestrant through a Compassionate Use Program, 29.9% experienced clinical benefits, including partial responses and stable disease for over 6 months.

Fulvestrant was well tolerated, with only 1.5% of patients discontinuing treatment due to adverse events, indicating its safety and potential as an effective option for patients who have not responded to previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant (Faslodex) in advanced breast cancer: clinical experience from a Belgian cooperative study. Neven, P., Paridaens, R., Pelgrims, G., et al.[2018]

In a study involving 587 postmenopausal women with advanced breast cancer, fulvestrant showed similar efficacy to tamoxifen in patients with hormone receptor-positive tumors, with no significant differences in time to progression (TTP) or objective response rates.

While tamoxifen had a slightly better overall efficacy in the general population, both treatments were well tolerated, indicating that fulvestrant can be a viable option for patients with ER+ and/or PgR+ tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. Howell, A., Robertson, JF., Abram, P., et al.[2022]

Fulvestrant, an estrogen receptor antagonist, was effective in treating advanced breast cancer in postmenopausal women, showing an overall clinical benefit in 39% of the 339 patients studied, with better outcomes when used as a first-line treatment.

The treatment was well tolerated, with only 5% of patients experiencing adverse events, and it was particularly beneficial for patients with tumors expressing both estrogen and progesterone receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant ("Faslodex"): clinical experience from the Compassionate Use Programme. Steger, GG., Gips, M., Simon, SD., et al.[2018]

In a study involving 451 postmenopausal women with advanced breast cancer, fulvestrant was found to be as effective as anastrozole in terms of time to progression, with median times of 5.5 months for fulvestrant and 5.1 months for anastrozole.

Both treatments were well tolerated, with low withdrawal rates due to adverse events (3.2% for fulvestrant and 1.3% for anastrozole), indicating that fulvestrant is a safe and effective option for patients who have progressed on prior endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. Howell, A., Robertson, JF., Quaresma Albano, J., et al.[2022]

Fulvestrant was well tolerated and provided clinical benefit to 21% of heavily pre-treated postmenopausal women with advanced breast cancer, with 42% achieving stable disease for at least 12 weeks.

The efficacy of fulvestrant was similar whether given after disease progression or as maintenance therapy, with a median time to progression of 3 months and no significant toxicities reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant in heavily pre-treated patients with advanced breast cancer: results from a single compassionate use programme centre. Catania, C., Ascione, G., Adamoli, L., et al.[2018]

Faslodex (fulvestrant) is a novel selective estrogen receptor down-regulator (SERD) that effectively targets and degrades the estrogen receptor, offering a new treatment option for advanced breast cancer, especially in cases where tumors have become resistant to tamoxifen.

Unlike tamoxifen, which can lead to resistance and has risks such as endometrial carcinoma, Faslodex provides a 'pure' antiestrogen effect without agonistic activity, making it a promising alternative for both advanced and early breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Faslodex(TM) for the treatment of breast cancer. Smolnikar, K.[2019]

In a study of 400 postmenopausal women with advanced breast cancer, fulvestrant was found to be as effective as anastrozole in delaying disease progression, with a median time to progression of 5.4 months for fulvestrant compared to 3.4 months for anastrozole.

Fulvestrant also demonstrated a significantly longer duration of response in patients who responded to treatment, with a median duration of 19.0 months compared to 10.8 months for anastrozole, indicating it may provide a more sustained benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial. Osborne, CK., Pippen, J., Jones, SE., et al.[2022]

In a study of 54 postmenopausal women with metastatic breast cancer, fulvestrant demonstrated clinical benefit in 38.9% of patients, with a median time to progression of 6.4 months, indicating its efficacy even after multiple prior treatments.

Fulvestrant was well tolerated, with no severe toxicities (grade 3/4) reported, suggesting it is a safe option for patients with advanced breast cancer who have limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant ('Faslodex') in heavily pretreated postmenopausal patients with advanced breast cancer: single centre clinical experience from the compassionate use programme. Mlineritsch, B., Psenak, O., Mayer, P., et al.[2018]

Fulvestrant is a novel estrogen receptor antagonist used for the palliative treatment of advanced breast cancer in postmenopausal women, and it has no known agonist effects, making it a unique option for therapy.

The drug is well tolerated with mild gastrointestinal symptoms being the most common side effect, and it is administered as a once-a-month intramuscular injection, providing a convenient treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant antiestrogen for treatment of breast cancer. Hancock, CM.[2018]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS1123

TWT-203: Phase 1b/2 dose-confirming study of CFI ... A first-in-human phase 1 study of CFI-402257 administered orally as a single agent, demonstrated a tolerable safety profile and evidence of clinical activity

2. pnas.org pnas.org/doi/10.1073/pnas.1700234114

Functional characterization of CFI-402257, a potent and ... We describe here the cellular and antitumor effects of CFI-402257, a potent and selective Mps1 kinase inhibitor. CFI-402257 shows strong antineoplastic activity ...

3. aacrjournals.org aacrjournals.org/cancerres/article/83/5_Supplement/P6-10-13/718061/Abstract-P6-10-13-An-update-to-a-Phase-I-trial-of

Abstract P6-10-13: An update to a Phase I trial of CFI-402257 ... CFI-402257 is a potent and highly selective inhibitor of TTK. Robust suppression of tumor growth was achieved upon oral dosing of single agent CFI-402257.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05251714

CFI-402257, a Potent and Selective TTK Inhibitor, in Solid ... 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 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9371652/

CFI-402257, a TTK inhibitor, effectively suppresses ... Our mass cytometry data illustrated the dynamic changes in the tumor-infiltrating immune populations after treatment with CFI-402257. Further, ...

6. aacrjournals.org aacrjournals.org/cancerres/article/84/9_Supplement/PO2-04-13/743562/Abstract-PO2-04-13-TWT-203-PHASE-1b-2-STUDY-OF-CFI

TWT-203: PHASE 1b/2 STUDY OF CFI-402257 AS ... A first-in-human phase 1 study of CFI-402257 (NCT02792465) demonstrated a tolerable safety profile when enrolled as a monotherapy in solid ...

7. asco.org asco.org/abstracts-presentations/ABSTRACT376176

Phase 1b/2 dose-confirming study of CFI-402257 as a ... A first-in-human phase 1 study of CFI-402257 administered orally as a single agent, demonstrated a tolerable safety profile and evidence of clinical activity in ...

8. onclive.com onclive.com/view/fda-grants-fast-track-designation-to-cfi-402257-for-er-her2-breast-cancer

FDA Grants Fast Track Designation to CFI-402257 for ER+ ... “CFI-402257 has shown early signs of durable activity with a manageable safety profile, as a monotherapy and in combination with fulvestrant in ...