BGB-21447 Combinations for Breast Cancer

Recruiting at 17 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: BeOne Medicines

Must be taking: GnRH agonists

Must not be taking: Bcl-2 inhibitors

Disqualifiers: Leptomeningeal disease, Brain metastases, others

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

Compensation: Varies

Number of Visits: 1

Duration: 6 to 9 months

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with HR+/HER2- metastatic breast cancer. It tests the safety and metabolism of BGB-21447, a drug targeting specific cancer cell proteins, when used with fulvestrant and possibly another drug, BGB-43395, which focuses on controlling cell growth. Participants should have previously received at least one treatment for advanced breast cancer, including hormonal therapy and CDK4/6 inhibitors. Those with breast cancer that has spread and who have tried other treatments may find this trial suitable. 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 this new therapy.

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, you must not have had prior exposure to Bcl-2 inhibitors, and you may need to continue or start ovarian function suppression if you are a female participant.

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

Research has shown that BGB-21447, a drug under investigation for breast cancer, is being studied to assess its safety when combined with other treatments. BGB-21447 is a Bcl-2 inhibitor, designed to prevent cancer cells from surviving. Detailed safety information is not yet available, as it is still in a phase 1 study, which focuses on evaluating safety and determining the optimal dose. Researchers are still identifying possible side effects.

The combination of BGB-21447 with BGB-43395, another investigational drug, is also in phase 1. Researchers are closely monitoring how well participants tolerate these drugs together and are vigilant for any unwanted side effects.

In summary, while specific safety data has not yet been published, the study's phase indicates that the treatment is in the early stages of safety testing. Participants will be closely monitored to identify and manage any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BGB-21447 for breast cancer because it offers a novel approach compared to standard treatments like hormonal therapies and chemotherapy. BGB-21447 is designed to be used alongside fulvestrant and potentially another agent, BGB-43395, which might enhance its effectiveness by targeting cancer cells in a new way. This combination could improve outcomes by tackling the cancer through multiple pathways, possibly overcoming resistance that sometimes develops with existing therapies. Additionally, the study explores how food intake affects the treatment, aiming to optimize its effectiveness regardless of meal timing, which is an innovative aspect not traditionally considered in breast cancer treatments.

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

Research has shown that BGB-21447, a new drug, is being tested for its potential to treat HR+/HER2- metastatic breast cancer. Past studies have demonstrated that combining CDK4/6 inhibitors with hormone therapy benefits patients, but cancer can eventually resist these treatments. BGB-21447 aims to overcome this resistance by targeting a protein called Bcl-2, which aids cancer cell survival. In this trial, some participants will receive BGB-21447 with fulvestrant, another cancer drug that has shown promise in lab studies by disrupting cancer cell survival mechanisms. Additionally, other participants will receive a combination of BGB-21447 with both fulvestrant and BGB-43395, another drug targeting cancer growth, which might enhance treatment effectiveness. These combinations are currently undergoing further testing to confirm their efficacy and safety. ^{2 4 6 7 8}

Who Is on the Research Team?

Study Director

Principal Investigator

BeOne Medicines

Are You a Good Fit for This Trial?

Adults with HR+/HER2- metastatic breast cancer who've had at least two prior treatments, including endocrine therapy and CDK4/6 inhibitors. Women must manage ovarian function suppression; men may need GnRH agonists. Participants should be relatively healthy (ECOG ≤ 1) and willing to use effective birth control during the study.

Inclusion Criteria

My breast cancer is HR+/HER2- and I've had at least 2 treatments for it, including hormone therapy and a CDK4/6 inhibitor.

I am a woman with breast cancer and will start or continue ovarian suppression.

I am a male willing to use hormone therapy if treated with certain breast cancer drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BGB-21447 in combination with fulvestrant, with or without BGB-43395, to assess safety and tolerability

6 to 9 months

Regular visits for dose escalation and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Long-term follow-up

Participants are monitored for long-term outcomes such as Objective Response Rate and Duration of Response

Approximately 12 months

What Are the Treatments Tested in This Trial?

Interventions

• BGB-21447
• BGB-43395

Trial Overview The trial is testing BGB-21447, a drug aimed at blocking a protein that helps cancer cells survive, combined with fulvestrant. It's also looking at adding another drug, BGB-43395, which inhibits enzymes involved in cell division. The goal is to see if these combinations are safe for patients.

How Is the Trial Designed?

Group I: Part 2: Dose Expansion, BGB-21447 + Fulvestrant Experimental Treatment 2 Interventions

Participants will receive BGB-21447 at the recommended dose(s) for expansion determined in Part 1A in combination with fulvestrant.

Group II: Part 1B: BGB-21447 + BGB-43395 + Fulvestrant Experimental Treatment 3 Interventions

Sequential cohorts of increasing dose levels of BGB-21447 will be evaluated in combination with fulvestrant and BGB-43395.

Group III: Part 1A: BGB-21447 + Fulvestrant Experimental Treatment 2 Interventions

Sequential cohorts of increasing dose levels of BGB-21447 will be evaluated in combination with fulvestrant.

Group IV: BGB-21447 + Fulvestrant Food Effect Substudy Experimental Treatment 2 Interventions

Participants will receive BGB-21447 at the recommended dose with a high-fat meal and under a fasted state in combination with fulvestrant.

Who Is Running the Clinical Trial?

BeOne Medicines

Lead Sponsor

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Published Research Related to This Trial

The rise in breast cancer brain metastases (BCBMs) is linked to improved systemic control of HER2+ breast cancer, highlighting the need for effective treatments that can cross the blood-brain barrier (BBB).

Preclinical studies suggest that inhibitors targeting the PI3K/AKT/mTOR signaling pathway, such as buparlisib and everolimus, may effectively treat BCBMs by penetrating the BBB and down-regulating cancer signaling, and are currently being tested in combination with trastuzumab in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PI3K pathway inhibitors for the treatment of brain metastases with a focus on HER2+ breast cancer. Peddi, PF., Hurvitz, SA.[2023]

In the MONALEESA-2 study involving 213 US patients with hormone receptor-positive, HER2-negative advanced breast cancer, ribociclib combined with letrozole significantly improved progression-free survival (PFS) to 27.6 months compared to 15.0 months with letrozole alone, indicating its efficacy as a first-line treatment.

The most common side effects of ribociclib included neutropenia (72%), nausea (69%), and fatigue (60%), highlighting the importance of monitoring for these adverse events during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Ribociclib With Letrozole in US Patients Enrolled in the MONALEESA-2 Study. Yardley, DA., Hart, L., Favret, A., et al.[2020]

Basal-like triple-negative breast cancer (TNBC) often has an overactive PI3K pathway, making it a target for treatment with BYL-719, a PIK3CA inhibitor that shows promise in combination therapies due to its low drug-drug interaction risk.

In studies using patient-derived xenograft models, BYL-719 was found to work synergistically with 20 different compounds, effectively reducing tumor growth, suggesting that these combinations could be beneficial for treating cancers with PIK3CA mutations or overactive PI3K pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovering Synergistic Compounds with BYL-719 in PI3K Overactivated Basal-like PDXs. Boyd, DC., Zboril, EK., Olex, AL., et al.[2023]

The BYLieve trial demonstrated that alpelisib combined with fulvestrant significantly improves progression-free survival (PFS) in patients with hormone receptor-positive, HER2-negative, PIK3CA-mutated advanced breast cancer, showing a median PFS of 7.3 months compared to 3.7 months in a matched real-world cohort.

This study is the first to compare the efficacy of alpelisib with fulvestrant against standard treatments in a real-world setting, confirming that the combination therapy is more effective than standard care after prior treatment with CDK4/6 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Alpelisib + Fulvestrant Compared with Real-World Standard Treatment Among Patients with HR+, HER2-, PIK3CA-Mutated Breast Cancer. Turner, S., Chia, S., Kanakamedala, H., et al.[2022]

The combination of everolimus, letrozole, and trastuzumab was found to be safe and showed promising anticancer activity in a study of 32 patients with treatment-refractory hormone receptor-positive, HER2-positive advanced cancers.

Partial responses were observed in five breast cancer patients, indicating potential effectiveness, while specific adverse events like hyperglycemia and mucositis were noted, helping to establish a recommended dose for future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Everolimus, Letrozole, and Trastuzumab in Patients with Hormone Receptor-positive Metastatic Breast Cancer or Other Solid Tumors. Ballhausen, A., Wheler, JJ., Karp, DD., et al.[2022]

The study established the recommended phase 2 doses (RP2D) for alpelisib (350 mg) and buparlisib (100 mg) when combined with tamoxifen and goserelin in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer, showing that both combinations were well-tolerated.

Patients treated with alpelisib experienced a longer progression-free survival of 25.2 months compared to 20.6 months for those on buparlisib, suggesting that alpelisib may be a more effective option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib Study of Alpelisib or Buparlisib Combined with Tamoxifen Plus Goserelin in Premenopausal Women with HR-Positive HER2-Negative Advanced Breast Cancer. Lu, YS., Lee, KS., Chao, TY., et al.[2021]

CB-103 demonstrated significant anti-tumor activity when combined with fulvestrant in endocrine-resistant ER+ breast cancer models, effectively reducing tumor volume in ESR1-mutant xenografts.

In triple-negative breast cancer (TNBC) models, CB-103 combined with paclitaxel significantly delayed tumor growth and inhibited cancer stem cell formation, suggesting its potential as a treatment option alongside standard chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy of CB-103, a First-in-Class Transcriptional Notch Inhibitor, in Preclinical Models of Breast Cancer. Vigolo, M., Urech, C., Lamy, S., et al.[2023]

The combination of buparlisib and letrozole was found to be safe for patients with metastatic ER-positive breast cancer, with a maximum-tolerated dose of 100 mg/day and manageable side effects like hyperglycemia and fatigue.

In this phase Ib study involving 51 patients, the treatment showed a clinical benefit rate of 31%, indicating some patients experienced significant disease control, regardless of their PIK3CA mutation status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stand up to cancer phase Ib study of pan-phosphoinositide-3-kinase inhibitor buparlisib with letrozole in estrogen receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. Mayer, IA., Abramson, VG., Isakoff, SJ., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06756932

Study Details | NCT06756932 | BGB-21447 (Bcl-2 Inhibitor ... While CDK4/6 inhibitors combined with endocrine therapy have improved outcomes for patients with HR+/HER2- metastatic breast cancer, patients eventually develop ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-00365

BGB-21447 (Bcl-2 Inhibitor) Combinations for Adults With ... therapy have improved outcomes for patients with HR+/HER2- metastatic breast cancer,. patients eventually develop progressive disease on these therapies and ...

3. trials.cancervic.org.au trials.cancervic.org.au/details/vctl_nct06756932

BGB-21447-102 - Victorian Cancer Trials Link This new study will check how safe and helpful a powerful anticancer drug called BGB-21447 (Bcl-2i) is. This drug will be tested in combination ...

4. withpower.com withpower.com/trial/phase-1-breast-neoplasms-2025-de882

BGB-21447 Combinations for Breast Cancer The safety of buparlisib (BGB-21447) has been evaluated in combination with other treatments for breast cancer, showing it is generally tolerable, but specific ...

5. trialstoday.org trialstoday.org/trial/NCT06756932

BGB-21447 (Bcl-2 Inhibitor) Combinations for Adults ... This is a dose escalation and dose expansion study to assess the safety and tolerability of BGB-21447 (a B-cell leukemia/lymphoma 2 inhibitor, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06756932

Study Details | NCT06756932 | BGB-21447 (Bcl-2 Inhibitor ... This new study will check how safe and helpful a potential anticancer drug called BGB-21447 (Bcl-2i) is. This drug will be tested in combination with ...

7. clinicaltrials.uihealthcare.org clinicaltrials.uihealthcare.org/studies/phase-1-study-investigate-safety-tolerability-pharmacokinetics-pharmacodynamics-and

Metastatic Breast Cancer - Clinical Trials - UI Health Care This new study will check how safe and helpful a potential anticancer drug called BGB-21447 (Bcl-2i) is. This drug will be tested in combination with ...

8. anzctr.org.au anzctr.org.au/Trial/Registration/TrialReview.aspx?id=23633&isClinicalTrial=True

ANZCTR - Registration Experimental: Part 2: Dose Expansion, BGB-21447 + Fulvestrant - Participants will receive BGB-21447 at the recommended dose(s) for expansion ...