BG-68501 + Fulvestrant for Breast Cancer

Recruiting at 40 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

138 Participants Needed

Trial Summary

What is the purpose of this trial?

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, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of BG-68501 in participants with advanced, nonresectable, or metastatic solid tumors as monotherapy and in combination with fulvestrant with or without BGB-43395, a selective CDK4 inhibitor, in adults with hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer (BC). The study will also identify a recommended dose for expansion (RDFE) for BG-68501 as monotherapy and in combination for subsequent disease directed studies. The study will be conducted in 2 parts: Part 1 (dose escalation and safety expansion) and Part 2 (dose expansion).

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.

What data supports the effectiveness of the drug BG-68501 + Fulvestrant for breast cancer?

Fulvestrant has shown effectiveness in treating postmenopausal women with hormone receptor-positive metastatic breast cancer, even after other treatments have failed. It has been observed to provide a durable response and limited side effects, making it a valuable option for patients with advanced breast cancer. ^{1 2 3 4 5}

Is the combination of BG-68501 (ETX-197) and Fulvestrant safe for humans?

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 site reactions and hot flushes. There is no specific safety data available for BG-68501 (ETX-197) in humans. ^{3 5 6 7 8}

What makes the drug BG-68501 + Fulvestrant unique for breast cancer treatment?

The combination of BG-68501 (ETX-197) with Fulvestrant is unique because it potentially offers a new approach by combining a novel agent with Fulvestrant, which is a pure estrogen receptor antagonist known for its effectiveness in hormone receptor-positive breast cancer. This combination may enhance the antitumor activity, especially in cases where cancer has progressed after other endocrine therapies. ^{3 4 5 8 9}

Research Team

Study Director

Principal Investigator

BeiGene

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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 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 III: 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 IV: 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+

Findings from Research

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]

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, 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 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 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 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]

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]

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]

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]

References

1. Japan pubmed.ncbi.nlm.nih.gov

Fulvestrant 500 mg in postmenopausal patients with metastatic breast cancer: the initial clinical experience. [2022]

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. 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]

4. England 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. [2022]

5. Cyprus pubmed.ncbi.nlm.nih.gov

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

6. Japan 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]. [2022]

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

9. Netherlands pubmed.ncbi.nlm.nih.gov

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