STX-478 + Fulvestrant for Advanced Breast Cancer

Recruiting at31 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Scorpion Therapeutics, Inc.

Must be taking: Fulvestrant, CDK4/6 inhibitors

Must not be taking: PI3K/AKT/mTOR inhibitors

Disqualifiers: Diabetes, Brain metastases, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called STX-478 to see if it can help treat advanced solid tumors and breast cancer. The study will look at how safe the drug is, how it behaves in the body, and if it can stop or slow down cancer growth. Some patients will receive just STX-478, while others will get it combined with another drug called fulvestrant, which is often used to treat advanced breast cancer.

Will I have to stop taking my current medications?

The trial requires a 'washout period' (time without taking certain medications) of up to 28 days for any local or systemic anticancer therapy before starting the study treatment. If you're on such medications, you may need to stop them before participating.

What data supports the effectiveness of the drug combination STX-478 and Fulvestrant for advanced breast cancer?

Fulvestrant has shown effectiveness in treating advanced breast cancer, especially in postmenopausal women whose cancer has progressed after other treatments. It has been effective in cases with estrogen receptor-positive and HER2-positive tumors, providing a clinical benefit in a significant number of patients. ^{1 2 3 4 5}

Is the combination of STX-478 and Fulvestrant safe for humans?

Fulvestrant, also known as Faslodex, has been used in various studies for advanced breast cancer and is generally well tolerated, with only a small percentage of patients experiencing mild side effects. However, there is no specific safety data available for the combination of STX-478 and Fulvestrant. ^{1 3 6 7 8}

What makes the drug STX-478 + Fulvestrant unique for advanced breast cancer?

STX-478 combined with Fulvestrant is unique because it pairs a new treatment (STX-478) with Fulvestrant, a well-established estrogen receptor antagonist, potentially offering a novel approach for patients with advanced breast cancer who have progressed on other therapies. This combination may provide a new option for those with hormone receptor-positive and HER2-positive breast cancer, where standard treatments have limited effectiveness. ^{1 3 5 8 9}

Research Team

Amar Patel, MD

Principal Investigator

Scorpion Therapeutics, Inc.

Eligibility Criteria

This trial is for adults with advanced solid tumors, including breast and gynecologic cancers, that have a specific mutation (PI3Kα). Participants must be in good physical condition (ECOG score of 0 or 1) and not have uncontrolled diabetes or recent treatments with certain inhibitors. They should not have other cancer types within the last two years or brain/spinal metastases.

Inclusion Criteria

My cancer has spread or can't be removed by surgery.

I am 18 years old or older.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

My tumor has specific genetic changes in PTEN and AKT.

My side effects from cancer treatments are mild or gone, except for hair loss or nerve issues.

I had a different type of cancer within the last 2 years.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive STX-478 as monotherapy or in combination with other antineoplastic agents

Varies by cohort

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Fulvestrant (Hormone Therapy)
• STX-478 (Other)

Trial Overview The study tests STX-478 alone and combined with Fulvestrant on patients with advanced solid tumors. It's divided into parts: one for STX-478 as monotherapy, another for combination therapy. The treatment follows a screening period and aims to assess safety, tolerability, and anti-tumor effects.

Participant Groups

Group I: Dose Selection/Expansion: Combination STX-478 + fulvestrant Experimental Treatment 2 Interventions

Cohort B: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Kα mutations

Group II: Dose Selection/Expansion Combination STX-478 + fulvestrant + CDK4/6 inhibitor Experimental Treatment 4 Interventions

Cohort C/D: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Ka mutations

Group III: Dose Expansion Experimental Treatment 1 Intervention

* Cohort A1: HR+/HER2- breast cancer expressing PI3Ka mutations * Cohort A2: Gynecologic cancers * Cohort A3: Head and Neck Squamous Cell Carcinoma * Cohorts A4/A5: Other solid tumors not included in Cohorts A1, A2, or A3 expressing PI3Kα mutations

Group IV: Dose Escalation (Advanced Solid Tumors) Experimental Treatment 1 Intervention

* Cohort A0: Advanced Solid tumors expressing PI3Kα mutations * Cohort A1: HR+ breast cancer expressing PI3Kα mutations

Who Is Running the Clinical Trial?

Scorpion Therapeutics, Inc.

Lead Sponsor

Trials

2

Recruited

520+

Findings from Research

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, 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 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]

Fulvestrant is an effective estrogen receptor antagonist for postmenopausal women with advanced breast cancer who have progressed after previous endocrine therapies, as demonstrated in a Compassionate Use Programme with diverse patient cases.

Clinical experience from the Compassionate Use Programme aligns with clinical trial data, indicating that fulvestrant is a valuable treatment option even for patients with challenging disease characteristics, such as visceral metastases and HER2-positive breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case studies of fulvestrant ("Faslodex") in postmenopausal women with advanced breast cancer. Abram, P., Maass, N., Rea, D., et al.[2018]

Fulvestrant is an effective estrogen antagonist for postmenopausal women with hormone-sensitive advanced breast cancer, particularly after they have progressed on other antiestrogen therapies, and it has recently been approved at a higher dose of 500 mg/month based on clinical trial results.

While fulvestrant alone is effective, combining it with growth factor signaling inhibitors may enhance its efficacy, and further research is needed to understand resistance mechanisms in patients who still respond to antiestrogen therapy after prior treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant in the management of postmenopausal women with advanced, endocrine-responsive breast cancer. Oakman, C., Moretti, E., Santarpia, L., et al.[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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical benefit of fulvestrant monotherapy in the multimodal treatment of hormone receptor and HER2 positive advanced breast cancer: a case series. [2020]

2. United States 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. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Fulvestrant ("Faslodex"): clinical experience from the Compassionate Use Programme. [2018]

4. United States 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. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Case studies of fulvestrant ("Faslodex") in postmenopausal women with advanced breast cancer. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Fulvestrant in the management of postmenopausal women with advanced, endocrine-responsive breast cancer. [2018]

7. Germany pubmed.ncbi.nlm.nih.gov

Fulvestrant 250 mg versus anastrozole for Chinese patients with advanced breast cancer: results of a multicentre, double-blind, randomised phase III trial. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Fulvestrant ('Faslodex') in pre-treated patients with advanced breast cancer: a single-centre experience. [2018]

9. Netherlands 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. [2018]