BTX-9341 + Fulvestrant for Breast Cancer

Recruiting at 5 trial locations

Overseen By Danette Powell

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Biotheryx, Inc.

Must be taking: Fulvestrant

Must not be taking: Anticoagulants

Disqualifiers: RB1 mutation, CNS metastasis, others

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

Compensation: Varies

Number of Visits: 56

82 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new drug, BTX-9341, both alone and with fulvestrant, a current breast cancer medication, for treating advanced hormone receptor-positive breast cancer. Researchers determine the best dose of BTX-9341 by gradually increasing it in early stages and then testing this dose with fulvestrant. Suitable candidates for this trial have advanced breast cancer that is hormone receptor-positive and HER2-negative and have previously tried treatments like chemotherapy or CDK4/6 inhibitors. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop your current medications. However, it mentions that participants must have been on prior endocrine and CDK4/6 inhibitor therapies for at least 6 months before progression, suggesting that some medications may need to be continued. Please consult with the trial investigators for specific guidance.

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

Research on BTX-9341 shows early results as it undergoes testing for safety in humans. The studies remain in the initial stages, so complete safety details are not yet available. In this first phase of testing, the primary focus is on understanding its safety, with close monitoring of any side effects.

Fulvestrant, already approved for treating breast cancer, is generally well-tolerated, with known side effects such as nausea and injection site pain. Researchers are examining how well people tolerate the combination of Fulvestrant and BTX-9341. Most current information comes from animal and lab studies, with human safety details expected from ongoing trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BTX-9341 for breast cancer because it introduces a novel approach by incorporating an oral capsule form that can be taken daily. Unlike standard treatments that often rely on intravenous administration, BTX-9341 offers a more convenient delivery method. Additionally, when combined with fulvestrant, which is already a well-established therapy, this combination targets cancer in a potentially more effective and synergistic way. This dual approach could offer enhanced anti-cancer effects compared to current standard therapies.

What evidence suggests that this trial's treatments could be effective for breast cancer?

Research has shown that BTX-9341 could be a promising treatment for breast cancer. Lab studies demonstrated that it reduced certain proteins (CDK4 and CDK6) by up to 85%. These proteins aid cancer cell growth, so reducing them might prevent the cancer from spreading. In animal tests, BTX-9341 slowed tumor growth and even caused tumors to shrink at certain doses. In this trial, some participants will receive BTX-9341 alone, while others will receive a combination of BTX-9341 and fulvestrant, a drug already used for breast cancer. These early findings suggest that BTX-9341, especially when combined with fulvestrant, could be effective against hormone receptor-positive breast cancer. ^{1 3 6 7 8}

Who Is on the Research Team?

Jeremy Barton, MD

Principal Investigator

Chief Medical Officer

Are You a Good Fit for This Trial?

This trial is for individuals with advanced or metastatic HR+/HER2- breast cancer. Participants should have a type of breast cancer that has spread and responds to hormones but not the HER2 protein. They will test BTX-9341 alone or with fulvestrant, which is already used for this cancer.

Inclusion Criteria

Able and willing to sign informed consent

My breast cancer has spread and is HR+/HER2-.

Meets all study requirements in the opinion of the Investigator

Exclusion Criteria

I have symptoms caused by cancer in my internal organs.

My cancer has spread to my brain or spinal cord.

My cancer has a mutation in the RB1 gene.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation (Part A)

Participants receive increasing doses of BTX-9341 alone or in combination with fulvestrant to determine the maximum tolerated dose (MTD) or minimum effective dose (MED)

Approximately 1 year

28-day cycles with regular monitoring

Dose Expansion (Part B)

Participants receive the selected dose of BTX-9341 in combination with fulvestrant to evaluate objective response rate

Approximately 18 months

28-day cycles with regular monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 28 days after last dose of BTX-9341

What Are the Treatments Tested in This Trial?

Interventions

• BTX-9341
• Fulvestrant

Trial Overview The study tests BTX-9341's safety and effectiveness, both on its own and combined with fulvestrant. It starts by giving small groups increasing doses of BTX-9341 (Part A), then moves to more people getting the best dose found plus fulvestrant (Part B).

How Is the Trial Designed?

Group I: BTX-9341 + fulvestrant (Part B) Experimental Treatment 2 Interventions

BTX-9341 capsule(s) administered orally QD in 28-day cycles and fulvestrant intermuscular injections on Day 15 and then once every 28 days

Group II: BTX-9341 + fulvestrant (Part A) Experimental Treatment 2 Interventions

BTX-9341 capsule(s) administered orally QD in 28-day cycles and fulvestrant intermuscular injections on Day 15 and then once every 28 days

Group III: BTX-9341 (Part A) Experimental Treatment 1 Intervention

BTX-9341 capsule(s) administered orally once daily (QD) in 28-day cycles

BTX-9341 is already approved in United States for the following indications:

Approved in United States as BTX-9341 for:

• None approved yet; currently in Phase 1 clinical trial for HR+/HER2- breast cancer

Who Is Running the Clinical Trial?

Biotheryx, Inc.

Lead Sponsor

Trials

2

Recruited

90+

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 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]

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 is an estrogen receptor downregulator being developed for the treatment of advanced breast cancer in postmenopausal women, with an NDA filed in the US for its use as a second-line therapy.

The drug shows potential not only for breast cancer but also for other estrogen-responsive tumors, such as uterine tumors, although further development for these indications has not been reported since the late 1990s.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant (AstraZeneca). Johnston, SR.[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]

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]

In a study involving 126 postmenopausal women with advanced breast cancer, fulvestrant demonstrated an objective response rate of 9.5% and a clinical benefit rate of 43.6%, indicating its efficacy as a treatment option after previous endocrine therapies.

Fulvestrant was well tolerated, with only six patients experiencing mild adverse events (grade I/II), suggesting it is a safe option for patients who have progressed on prior treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant ('Faslodex') in pre-treated patients with advanced breast cancer: a single-centre experience. Steger, GG., Bartsch, R., Wenzel, C., et al.[2018]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.3111

Characterization of BTX-9341, a bifunctional degrader ... Results: Breast cancer cell lines treated with BTX-9341 showed up to 85% degradation of CDK4 and CDK6 with DC50s <1nM. CDK4/6 phosphorylates ...

2. aacrjournals.org aacrjournals.org/clincancerres/article/31/12_Supplement/P4-11-02/752310/Abstract-P4-11-02-Characterization-of-BTX-9341-a

Abstract P4-11-02: Characterization of BTX-9341, a ... Breast cancer cell lines treated with BTX-9341 for 6 hours demonstrated up to 85% degradation of CDK4 and CDK6 with DC50s <1nM.

3. targetedonc.com targetedonc.com/view/phase-1-trial-of-btx-9341-in-hr-her2-breast-cancer-doses-first-patient

Phase 1 Trial of BTX-9341 in HR+/HER2– Breast Cancer ... In additional preclinical models, BTX-9341 administered orally showed in vivo CDK4/6 degradation and demonstrated benefits in antitumor activity ...

4. biotheryx.com biotheryx.com/wp-content/uploads/2023-1108-9341_SABCS_poster.pdf

Discovery of BTX-9341, a bifunctional degrader of CDK4 ... BTX-9341 exhibited more potent tumor growth inhibition in multiple HR+/HER2- xenograft models compared to CDK4/6i and induced tumor regression at some doses.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06515470

Study Details | NCT06515470 | Safety, Tolerability, ... The purpose of this study is to test BTX-9341 alone or in combination with fulvestrant (a currently marketed medication for breast cancer) in participants with ...

6. aacrjournals.org aacrjournals.org/clincancerres/article/31/12_Supplement/P4-08-17/753644/Abstract-P4-08-17-First-in-human-Phase-1-study-of

Abstract P4-08-17: First-in-human Phase 1 study of BTX-9341 ... This first-in-human (FIH), Phase 1 trial of BTX-9341 (BTX-9341-101) will be a multicenter, nonrandomized, open-label trial to evaluate the safety, tolerability ...

7. biotheryx.com biotheryx.com/biotheryx-announces-u-s-fda-clearance-of-investigational-new-drug-application-for-btx-9341-a-first-in-class-dual-bifunctional-degrader-of-cdk4-6/

About BTX-9341 The Company plans to initiate the Phase 1 clinical trial in the second half of 2024 and intends to enroll patients with HR+/HER2- breast cancer ...

8. clin.larvol.com clin.larvol.com/trial-detail/NCT06515470

Safety, Tolerability, Pharmacokinetics, and Preliminary ... Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of BTX-9341 in Advanced and/or Metastatic Breast Cancer. P1. Biotheryx, Inc. N=82. Recruiting.