BGB-43395 Combinations for Breast Cancer

Recruiting at 91 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: BeiGene

Must be taking: Endocrine therapy

Must not be taking: Systemic antibacterials

Disqualifiers: Uncontrolled diabetes, Brain metastases, others

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

Compensation: Varies

Number of Visits: Unknown

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find the optimal dose of a new drug, BGB-43395, which targets a protein involved in cell growth. Researchers seek to evaluate its effectiveness alone or with other treatments for individuals with certain advanced cancers, such as hormone receptor-positive breast cancer. They seek participants who have tried other treatments but need new options. Those with HR+ breast cancer should have undergone prior therapies, including hormone treatments and drugs targeting similar cell growth proteins. This trial offers a chance to explore promising new combinations that might improve outcomes for these cancer types. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, prior therapy with CDK4/6 inhibitors is required in some regions, and certain infections or conditions may exclude you from participation.

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

Research has shown that BGB-43395, a new drug under testing, has been mostly safe for people so far. In one study, nearly 94% of patients experienced side effects, but these were mostly mild, such as headaches or fatigue. This suggests that BGB-43395 is generally well-tolerated on its own.

The safety of BGB-43395 in combination with other drugs like fulvestrant or letrozole is still under investigation. Since fulvestrant and letrozole are already approved for similar conditions, combining them with BGB-43395 is expected to be safe for most people.

This trial is in an early phase, so researchers are still determining the safest dose. So far, evidence suggests that BGB-43395, whether used alone or with other drugs, is generally safe for humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BGB-43395 for breast cancer because it targets cancer cells in a potentially more precise way compared to current hormone therapies like tamoxifen or anastrozole. Unlike traditional options, BGB-43395 is being tested both as a standalone treatment and in combination with other drugs such as fulvestrant, letrozole, and elacestrant, which could enhance its effectiveness. This combination approach aims to boost the body's response to treatment, offering hope for improved outcomes in hormone receptor-positive breast cancer.

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

Research has shown that BGB-43395, a drug targeting a protein involved in cell growth, produced promising results in early lab studies. This drug may help stop cancer cells from multiplying. In lab tests, BGB-43395 was effective against a type of breast cancer that is hormone receptor positive and HER2 negative. This trial tests BGB-43395 both as a monotherapy and in combination with other breast cancer drugs like fulvestrant or letrozole to determine if these combinations can improve outcomes for breast cancer and other tumors. Early results suggest these treatments could be effective, but more research is needed to confirm these findings in people. ^{4 6 7 8 9}

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 solid tumors, like HR+ breast cancer or non-small cell lung cancer, that rely on CDK4. Participants must have tried standard treatments without success and be in good physical condition (ECOG ≤ 1). Women with metastatic HR+/HER2- breast cancer should be postmenopausal or suppressing ovarian function.

Inclusion Criteria

I have tried and not responded to or couldn't tolerate standard treatments.

I have HR+/HER2- breast cancer and have been treated with endocrine therapy and a CDK4/6 inhibitor.

I am a woman with advanced HR+/HER2- breast cancer and am either postmenopausal or receiving treatment to suppress ovarian function.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Sequential cohorts of increasing dose levels of BGB-43395 are evaluated as monotherapy and in combination with either fulvestrant or letrozole to assess for safety and tolerability

Up to approximately 60 months

Dose Expansion

The recommended dose for expansion (RFDE) for BGB-43395 in combination with fulvestrant or letrozole is evaluated in HR+ breast cancer and selected tumor-specific cohorts

Up to approximately 60 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BGB-43395
• Fulvestrant
• Letrozole

Trial Overview The study tests BGB-43395 alone or combined with fulvestrant or letrozole in patients with certain cancers. It aims to find the best dose of BGB-43395 by gradually increasing amounts and observing effects in different groups of participants.

How Is the Trial Designed?

Group I: Dose Expansion Experimental Treatment 3 Interventions

Phase 1b: The recommended dose for expansion (RFDE) for BGB-43395 (in combination with fulvestrant or letrozole) from Phase 1a will be evaluated in HR+ breast cancer and selected tumor-specific cohorts.

Group II: Dose Escalation and Safety Expansion Experimental Treatment 4 Interventions

Phase 1a: Sequential cohorts of increasing dose levels of BGB-43395 will be evaluated as monotherapy and in combination with either fulvestrant, letrozole, or elacestrant to assess for safety and tolerability.

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Published Research Related to This Trial

Metastatic breast cancer, particularly in HER2-positive and triple-negative subtypes, poses a significant risk of brain metastases, which are a leading cause of mortality in these patients.

Recent advancements in treatment options for brain metastases, including targeted therapies, immunotherapies, and improved radiation techniques, show promise in improving outcomes for patients with breast cancer brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging treatment strategies for breast cancer brain metastasis: from translational therapeutics to real-world experience. Ren, D., Cheng, H., Wang, X., et al.[2020]

This study identified a promising combination therapy for basal-like triple-negative breast cancer (TNBC) using KPT-330, an XPO1 inhibitor, and GSK2126458, a PI3K/mTOR inhibitor, which significantly reduced tumor burden in mouse models compared to single-agent treatments.

XPO1 was found to be overexpressed in basal-like TNBC cell lines and patient samples, correlating with increased tumor proliferation and metastasis, suggesting that targeting XPO1 could be a key strategy in treating this aggressive cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of nuclear export inhibitor-based combination therapies in preclinical models of triple-negative breast cancer. Rashid, NS., Hairr, NS., Murray, G., et al.[2021]

Oncolytic adenoviruses (OAds) represent a promising new therapeutic strategy for treating triple-negative breast cancer (TNBC), which is particularly aggressive and often resistant to standard treatments. Preclinical studies have shown that OAds can selectively target and destroy cancer cells while sparing normal cells, enhancing the potential for improved patient outcomes.

Combining OAds with existing treatments, such as PARP inhibitors like Olaparib and immune checkpoint antibodies, has demonstrated enhanced anti-tumor effects, suggesting that these combinations could lead to more effective therapies for women with TNBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Triple Negative Breast Cancer With Oncolytic Adenoviruses. Green-Tripp, G., Nattress, C., Halldén, G.[2022]

Recent advancements in understanding how breast cancer develops resistance to hormone therapies have led to new clinical trials that combine hormonal treatments with biological agents to improve outcomes for patients with ER+ breast cancer.

Despite promising results in laboratory studies, many of these combination therapies have not performed as well in clinical trials, highlighting the need for ongoing research to identify which patients will benefit most from these tailored treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trials update: endocrine and biological therapy combinations in the treatment of breast cancer. Leary, AF., Sirohi, B., Johnston, SR.[2021]

Triple positive breast cancers (TPBC), which express both HER-2 and hormone receptors, show unique biological characteristics that affect treatment efficacy, particularly leading to decreased effectiveness of hormonal therapies compared to HER-2-negative patients.

The study highlights the potential for improved outcomes in TPBC through tailored treatment strategies, including combinations of anti-HER-2 agents with hormonal therapy and other targeted therapies, as well as the importance of distinguishing between HER-2-positive subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic significance of hormone receptor positivity in patients with HER-2 positive breast cancer. Kolarova, I., Vanasek, J., Odrazka, K., et al.[2020]

In a study of 332 ductal breast cancer patients, the phosphorylation of the androgen receptor at ser515 (AR-515) combined with pERK1/2 was linked to improved cancer-specific survival and better tumor characteristics in estrogen receptor-positive (ER+) tumors.

Conversely, in triple negative breast cancer (TNBC) patients, AR-515 phosphorylation was associated with poorer cancer-specific survival, suggesting it may play a role in inflammation regulation and could serve as a prognostic marker and therapeutic target for TNBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phosphorylation of androgen receptors at serine 515 is a potential prognostic marker for triple negative breast cancer. Roseweir, AK., McCall, P., Scott, A., et al.[2018]

Triple-negative breast cancer (TNBC) is a challenging subtype of breast cancer that does not respond to hormonal or anti-HER2 therapies, making chemotherapy the standard treatment despite its limited effectiveness.

Recent advancements in treatment options, such as immune checkpoint inhibitors for PD-L1+ tumors and PARP inhibitors for BRCA-mutated tumors, show promise, but responses are limited and often lead to resistance, highlighting the need for ongoing research into new therapies and combination strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triple‑negative breast cancer therapy: Current and future perspectives (Review). Won, KA., Spruck, C.[2021]

Triple-negative breast cancer (TNBC) currently lacks targeted therapy options, relying primarily on chemotherapy, which is generally more effective for TNBC than for other breast cancer subtypes.

Recent research highlights the potential for targeted therapies in TNBC, driven by the subtype's genetic heterogeneity, suggesting that combinatorial treatments could improve outcomes for the 80% of patients who do not achieve a complete response to chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triple-negative breast cancer and the potential for targeted therapy. Jhan, JR., Andrechek, ER.[2018]

CD8-positive tumors in triple-negative breast cancer (TNBC) patients are more likely to benefit from immunotherapy, and targeting angiogenesis can enhance the effectiveness of checkpoint inhibitors.

In a phase II trial involving 48 patients, a combination of famitinib, camrelizumab, and chemotherapy achieved an impressive objective response rate of 81.3% and a median progression-free survival of 13.6 months, with no treatment-related deaths reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined angiogenesis and PD-1 inhibition for immunomodulatory TNBC: concept exploration and biomarker analysis in the FUTURE-C-Plus trial. Wu, SY., Xu, Y., Chen, L., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06120283

Study Details | NCT06120283 | BGB-43395 Alone or as ... This is a dose escalation and dose expansion study to compare how well BGB-43395, a selective cyclin-dependent kinase 4 (CDK4) inhibitor, works as monotherapy ...

2. beonemedinfo.com beonemedinfo.com/CongressDocuments/Zhu_BGB-43395_SABCS_Poster_2024.pdf

Preclinical characterization of BGB-43395, a potential best- ... As a result, BGB-. 43395 showed greater anti-proliferative activity in HR+HER2- BC cell lines as well as other cancer cell lines including prostate, ovarian, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06253195

Study Details | NCT06253195 | BGB-43395 Alone or as ... This is an open-label, multicenter, phase 1a/1b clinical study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary ...

4. oncologypipeline.com oncologypipeline.com/apexonco/pivotal-push-beigene

A pivotal push from BeiGene | ApexOnco Meanwhile, BeiGene's shot at CDK4-specific inhibition, BGB-43395, only started phase 1 in December 2023, and this study has so far yielded only ...

5. ascopubs.org ascopubs.org/doi/10.1200/EDBK-25-473372

After a CDK4/6 Inhibitor: State of the Art in Hormone ... The SOLAR-1 trial demonstrated significantly improved median PFS (11 v 5.7 months, HR, 0.65, 95% CI, 0.50 to 0.85) and numerically improved overall survival ( ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06120283

Study Details | NCT06120283 | BGB-43395 Alone or as ... This is a dose escalation and dose expansion study to compare how well BGB-43395, a selective cyclin-dependent kinase 4 (CDK4) inhibitor, works as ...

7. aacrjournals.org aacrjournals.org/clincancerres/article/31/12_Supplement/P4-10-20/752580/Abstract-P4-10-20-First-in-human-phase-1a-dose

First-in-human phase 1a, dose-escalation study of BGB-43395 ... To date, BGB-43395 has been safe and tolerable, supporting continued development. The dose-escalation phase is currently ongoing. Citation ...

8. beonemedinfo.com beonemedinfo.com/CongressDocuments/Yap_BGB-43395-101_SABCS_Poster_2024.pdf

First-in-human phase 1a, dose-escalation study of BGB- ... Safety. • TEAEs occurred in 61/65 (93.8%) patients overall, and were primarily grades (gr) 1 and 2 (Table 2). • For all 65 patients, ...

9. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/441397

BGB-43395 Alone or as Part of Combination Therapies in ... This is a dose escalation and dose expansion study to compare how well BGB-43395, a selective cyclin-dependent kinase 4 (CDK4) inhibitor, ...