STX-478 + Fulvestrant for Advanced Breast Cancer

(PIKALO-1 Trial)

Recruiting at 93 trial locations

Overseen By Physicians interested in becoming principal investigators please contact

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Eli Lilly and Company

Must be taking: Fulvestrant, CDK4/6 inhibitors

Must not be taking: PI3K/AKT/mTOR inhibitors

Disqualifiers: Diabetes, Brain metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Varies by cohort

720 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called STX-478 to determine its safety and effectiveness for people with advanced cancers, particularly those with a PI3Kα mutation, a specific genetic change in the cancer. The trial includes different parts: one examines STX-478 alone, while others combine it with treatments like fulvestrant (a hormone therapy) or CDK4/6 inhibitors, especially for hormone receptor-positive breast cancer. Suitable candidates are those with advanced cancer that cannot be surgically removed and have a PI3Kα mutation in their tumor. As a Phase 1/Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

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.

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

Research shows that STX-478 is generally safe for patients, particularly those with certain genetic changes in advanced solid tumors and breast cancer. It tends to cause fewer metabolism-related side effects compared to similar treatments.

When combined with fulvestrant, a drug already used for advanced breast cancer, STX-478 continues to show promise. Fulvestrant is usually well-tolerated, with only a small number of patients experiencing significant side effects. Together, these treatments have been studied for safety, and early results suggest they work well without major problems.

Overall, the available data provides a positive outlook on the safety of STX-478, whether used alone or with fulvestrant. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about STX-478 because it offers a targeted approach for treating advanced breast cancer by focusing on PI3Kα mutations, which are often implicated in cancer growth. While many current treatments for breast cancer, such as hormone therapies and chemotherapy, work broadly, STX-478 specifically inhibits the PI3Kα pathway. This specificity can potentially lead to more effective treatments with fewer side effects. Additionally, combining STX-478 with fulvestrant or endocrine therapies and CDK4/6 inhibitors could enhance its effectiveness, providing a more robust attack against cancer cells while sparing healthy ones.

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

Research has shown that STX-478, one of the treatments in this trial, may help treat solid tumors with certain mutations. One study found that the drug helped shrink tumors in 21% of patients. It performs as well as or better than similar treatments, but with fewer side effects like insulin resistance.

In this trial, some participants will receive a combination of STX-478 and fulvestrant, a drug already proven effective for advanced breast cancer. This combination might be even more effective against certain types of breast cancer. The trial aims to provide a more manageable treatment option with potentially better results, offering hope for improved outcomes for people with these specific cancer mutations. ^{1 2 4 5 6}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

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

My tumor has a PI3Kα mutation confirmed by an approved test.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Fulvestrant
• STX-478

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.

How Is the Trial Designed?

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 Experimental Treatment 7 Interventions

STX-478 + Endocrine therapy + CDK4/6 inhibitor Cohort C/D/E: 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 * Cohort A6: Endometrial cancer

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?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Scorpion Therapeutics, Inc.

Lead Sponsor

Trials

2

Recruited

520+

Published Research Related to This Trial

Fulvestrant, an estrogen receptor antagonist, shows promising efficacy in treating metastatic ER positive and HER2 positive breast cancer, even after patients have progressed on anti-HER2 therapies, with reported response durations of up to 38 months.

The treatment is associated with limited toxicity, making it a valuable option for patients with extensive metastases, including skin and brain, highlighting the need for further research to define its role in comprehensive breast cancer management.

NCBI (Pubmed)

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. Rusz, O., Kószó, R., Dobi, Á., et al.[2020]

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 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 involving 234 postmenopausal women with advanced breast cancer, fulvestrant (250 mg/month) and anastrozole (1 mg/day) showed similar efficacy, with median time to progression of 110 days for fulvestrant compared to 159 days for anastrozole, although this difference was not statistically significant.

Both treatments were well tolerated, with very few patients withdrawing due to adverse events, indicating that fulvestrant is a safe option comparable to anastrozole for patients who have progressed on prior endocrine therapy.

NCBI (Pubmed)

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. Xu, B., Jiang, Z., Shao, Z., 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 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 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 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, 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.

aacrjournals.org

aacrjournals.org/clincancerres/article/31/12_Supplement/PS7-02/753566/Abstract-PS7-02-First-in-human-results-of-STX-478

Abstract PS7-02: First-in-human results of STX-478, a mutant ...

Results: As of June 21st, 2024, 61 patients (29 HR+/HER2- BC, 32 other solid tumors) were treated at STX-478 monotherapy doses of 20 mg to 160 ...

2.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534%2824%2903846-8/fulltext

LBA27 First-in-human results of STX-478, a mutant- ...

At 40mg dose, STX-478 achieved target coverage several fold higher than other PI3Kα inhibitors. In 43 evaluable patients, the confirmed/unconfirmed ORR was 21%; ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10618743/

STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares ...

The efficacy of STX-478 is similar or superior to high-dose alpelisib across PI3Kα-mutant tumor xenografts while sparing insulin resistance (p.o., oral ...

4.

onclive.com

onclive.com/view/stk-478-may-be-an-effective-tolerable-treatment-alternative-in-pik3ca-mutant-breast-and-gynecologic-cancers

STK-478 May Be an Effective, Tolerable Treatment ...

The next-generation PI3Kα inhibitor STX-478 is associated with reduced metabolic toxicities and a favorable safety profile in PIK3CA-mutant breast and ...

5.

cancernetwork.com

cancernetwork.com/view/stx-478-yields-efficacy-tolerability-in-pi3k-mutated-advanced-solid-tumors

STX-478 Yields Efficacy, Tolerability in PI3K-Mutated ...

STX-478 showed efficacy in patients with advanced solid tumors regardless of whether they had kinase domain or helical PI3K mutations.

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07174336

A Study of LY4064809 With Other Anti-Cancer Treatments ...

The purpose of the study is to assess the efficacy and safety of the addition of LY4064809 to other anti-cancer drugs as first treatment for ...