BG-68501 + Fulvestrant for Breast Cancer

Recruiting at 50 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: BeiGene

Must be taking: GnRH agonists

Must not be taking: CDK2 inhibitors

Disqualifiers: Uncontrolled diabetes, Brain metastasis, others

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

Compensation: Varies

Number of Visits: Unknown

258 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called BG-68501 (also known as ETX-197), both alone and with other medicines, for individuals with advanced breast cancer unresponsive to current treatments. The researchers aim to determine the treatment's safety, its effects on the body, and the appropriate dose for future studies. They seek participants with hormone receptor-positive (HR+)/HER2-negative breast cancer who have already tried treatments like hormone therapy and CDK4/6 inhibitors. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it does mention that participants must not have had prior therapy selectively targeting CDK2 inhibition. It's best to discuss your current medications with the trial team to get a clear answer.

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

Research has shown that BG-68501 is under study to determine its safety when used alone or with other drugs like fulvestrant. In early studies, researchers are assessing how well individuals tolerate BG-68501 by itself, specifically checking for any harmful effects or side effects.

When combined with fulvestrant, studies also focus on safety. Fulvestrant is generally considered safe, with mild side effects such as injection site pain, which reassures those considering participation in trials with this combination.

For the combination of BG-68501 with fulvestrant and BGB-43395, researchers are still gathering safety information. This trial is in its initial phase, marking the first time these drugs are tested together in humans. The results will guide future use of these drugs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BG-68501 for breast cancer because it offers a new mechanism of action compared to current treatments. While many existing therapies, like hormone blockers and chemotherapy, target hormone receptors or rapidly dividing cells, BG-68501 works differently by targeting a novel pathway in cancer cell growth. Additionally, the combination of BG-68501 with fulvestrant and another investigational drug, BGB-43395, may enhance its effectiveness, potentially offering a more comprehensive approach to fighting breast cancer. This combination strategy could provide better outcomes for patients, making it a promising option in the fight against breast cancer.

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

Research shows that BG-68501, a new drug under investigation in this trial, may help fight breast cancer. Early studies found that BG-68501 could slow cancer growth, especially when other treatments failed. In this trial, some participants will receive BG-68501 alone, while others will receive it with fulvestrant, a drug that treats a common type of breast cancer in postmenopausal women. The results of using BG-68501 with fulvestrant have been promising. Fulvestrant has already succeeded in similar situations. Initial tests on animals showed that BG-68501 worked well on its own in tough-to-treat cancers, suggesting it might be helpful for people too. Overall, while it's still early, these findings offer hope for those with this type of breast cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Study Director

Principal Investigator

BeiGene

Are You a Good Fit for This Trial?

This trial is for adults with advanced-stage tumors, including breast, ovarian, endometrial, prostate, stomach cancers and SCLC. They must have tried standard treatments without success or be unable to tolerate them. Women with certain types of breast cancer need hormone suppression or be postmenopausal. Participants should be relatively healthy otherwise (ECOG ≤ 1) and have measurable disease.

Inclusion Criteria

My organs are working well.

My cancer is advanced or has spread and may respond to treatments targeting CDK2.

Participants with advanced solid tumors must have measurable disease per RECIST 1.1

Exclusion Criteria

My diabetes is not well-managed.

I have had a stem cell or organ transplant in the past.

I have had hepatitis B or currently have hepatitis C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation and Safety Expansion

Sequential cohorts of increasing dose levels of BG-68501 are evaluated as monotherapy and in combination with fulvestrant and BGB-43395

Up to approximately 24 months

Dose Expansion

The recommended dose for expansion (RDFE) for BG-68501 is evaluated in selected tumor cohorts

Up to approximately 20 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6-12 months

What Are the Treatments Tested in This Trial?

Interventions

• BG-68501

Trial Overview The study tests BG-68501, a new drug aimed at stopping tumor growth by inhibiting CDK2—a protein that helps cancer cells multiply. It's given in two parts: first to find the safest dose (dose escalation), then to see how well it works at this dose (dose expansion). The trial also includes Fulvestrant for comparison.

How Is the Trial Designed?

Group I: Part 2: Dose Expansion Experimental Treatment 3 Interventions

The RFDE for BG-68501 (as monotherapy and in combination with fulvestrant and BGB-43395) from Part 1 will be evaluated in selected tumor cohorts.

Group II: Part 1: Food Effect Evaluation Experimental Treatment 2 Interventions

Participants will receive BG-68501 at a dose level that is determined safe and tolerable to evaluate food effect. Food effect may also be evaluated for BG-68501 in combination with fulvestrant.

Group III: Part 1 Part C: Dose Escalation and Safety Expansion (BG-68501 + Fulvestrant + BGB-43395) Experimental Treatment 3 Interventions

Sequential cohorts of increasing dose levels of BG-68501 will be evaluated in combination with fulvestrant and BGB-43395.

Group IV: Part 1 Part B: Dose Escalation (BG-68501 + Fulvestrant) Experimental Treatment 2 Interventions

Sequential cohorts of increasing dose levels of BG-68501 will be evaluated in combination with fulvestrant.

Group V: Part 1 Part A: Dose Escalation and Safety Expansion (BG-68501 Monotherapy) Experimental Treatment 1 Intervention

Sequential cohorts of increasing dose levels of BG-68501 will be evaluated as monotherapy.

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Published Research Related to This Trial

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]

In a study of 86 postmenopausal patients with ER-positive metastatic breast cancer, 500 mg of fulvestrant demonstrated a clinical benefit rate of 36.0%, indicating its efficacy in managing the disease.

Patients who had not previously undergone endocrine therapy showed significantly prolonged median progression-free survival (mPFS) of 6.5 months, suggesting that fulvestrant is particularly effective when used as a first-line treatment in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of fulvestrant in treating postmenopausal patients with estrogen receptor-positive metastatic breast cancer and prognostic analysis. Li, T., Jiao, L.[2021]

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 490 women with hormone receptor-positive metastatic breast cancer, fulvestrant 500 mg demonstrated significant effectiveness, with a median overall survival of 26.8 months, particularly better in patients receiving it as a first-line treatment (32.4 months).

The presence of liver metastasis was identified as a negative prognostic factor, impacting both progression-free survival and overall survival, highlighting the importance of disease characteristics in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of treatment and outcome with 500-mg fulvestrant in postmenopausal women with hormone receptor-positive/HER2-negative metastatic breast cancer: a real-life multicenter Italian experience. Palumbo, R., Sottotetti, F., Quaquarini, E., et al.[2022]

In a study of 69 postmenopausal women with advanced, recurrent ER-positive breast cancer, 500 mg of fulvestrant showed a favorable objective response rate of 24.6% and a clinical benefit rate of 49.2%.

The treatment was generally safe, with mild to moderate adverse effects like injection site reactions and hot flushes, and it was particularly effective in patients without a history of prior treatments or visceral metastasis, with a median overall survival of 794 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety of the Selective Estrogen Receptor Down-Regulator "Fulvestrant" in Japanese Patients with Advanced, Recurrent, ER-Positive Postmenopausal Breast Cancer]. Egawa, C., Okishiro, M., Takatsuka, Y.[2022]

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 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 of 117 postmenopausal women with hormone receptor-positive metastatic breast cancer, fulvestrant 500 mg demonstrated an objective response rate of 8.5% and a clinical benefit rate of 41.9%, indicating its efficacy after previous endocrine therapies.

The median time to progression (TTP) was 6.1 months, with factors such as the absence of liver metastases and longer duration of first-line endocrine therapy positively correlating with TTP, suggesting that fulvestrant may be particularly beneficial for patients with specific treatment histories.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant 500 mg in postmenopausal patients with metastatic breast cancer: the initial clinical experience. Ishida, N., Araki, K., Sakai, T., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.3115

breast cancer and other advanced solid tumors: First ... We present dose-escalation data of BG-68501 as monotherapy or in combination with fulvestrant in pts with HR+/HER2- metastatic breast cancer (BC) and advanced ...

2. aacrjournals.org aacrjournals.org/clincancerres/article/31/12_Supplement/P4-12-29/753025/Abstract-P4-12-29-ETX-197-BG-68501-a-potential

Abstract P4-12-29: ETX-197/BG-68501, a potential best-in ... These data suggest that ETX-197 has the potential to be a best-in class CDK2 inhibitor for the treatment of cancer with CCNE amplification or ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06257264

NCT06257264 | A Study to Examine the Safety of Different ... This study is a first-in-human (FIH), Phase 1a/1b study of BG-68501, a cyclin-dependent kinase-2 inhibitor (CDK2i), to assess the safety, tolerability, ...

4. onclive.com onclive.com/view/a-first-in-human-phase-1a-b-dose-escalation-expansion-study-of-bg-68501-a-selective-cdk2-inhibitor-as-monotherapy-or-in-combination-with-fulvestrant-for-patients-with-hr-her2-breast-cancer-and-other-advanced-solid-tumors-first-disclosure-of-clinical-data

A First-in-Human, Phase 1a/b, Dose-Escalation/Expansion ... Van Tine, MD, PhD, presents results from the first-in-human Phase 1a trial of BG-68501, a selective CDK2 inhibitor, showing early signs of ...

5. firstwordpharma.com firstwordpharma.com/story/5920329

Ensem Therapeutics To Present Preclinical Data for ... ETX-197/BG-68501 demonstrated single agent efficacy in a breast cancer xenograft model that had acquired resistance to a CDK4/CDK6 inhibitor.

6. withpower.com withpower.com/trial/phase-1-endometrial-neoplasms-1-2024-54977

BG-68501 + Fulvestrant for Breast Cancer The safety data available is primarily for Fulvestrant, which has been shown to be generally safe in humans, with mild to moderate side effects like injection ...