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BGB-21447 (Bcl-2 Inhibitor) Combinations for Adults With Hormone-Receptor Positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Metastatic Breast Cancer

PHASE1RECRUITING

The purpose of this study is to assess the safety and tolerability of BGB-21447 (a B-cell leukemia/lymphoma 2 inhibitor, Bcl-2i) in combination with fulvestrant, with or without BGB-43395 (cyclin-dependent kinase 4 inhibitor, CDK4i), in adults with HR+/HER2- metastatic breast cancer.

Study details:

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 fulvestrant, with or without BGB-43395 (CDK4i), in adults with metastatic breast cancer. HR+/HER2- tumors account for approximately 70% of all breast cancers and are responsible for most breast cancer-related deaths.

While CDK4/6 inhibitors combined with endocrine therapy have improved outcomes for patients with HR+/HER2- metastatic breast cancer, patients eventually develop progressive disease on these therapies and require new treatments. BGB-21447 is an oral drug that is highly potent and selectively stops a protein called B-cell lymphoma-2 (Bcl-2). Bcl-2 proteins are often overexpressed in some cancers (like HR+ breast cancer) by keeping the cancer cells from dying.

By disrupting this pathway, antitumor effects can be achieved. BGB-43395 is an oral drug that selectively stops a protein called cyclin-dependent kinase 4 (CDK4). CDK4 is a type of protein that regulates cell growth and division in your body.

CDK4 inhibition is believed to have antitumor effects. Fulvestrant is a treatment that blocks estrogen receptors and reduces estrogen production. Fulvestrant has been approved to treat hormone receptor positive metastatic breast cancer to help stop the cancer cells from growing.

This combination might be a good way to fight cancer, aiming to give patients the best possible treatment. The study is designed to see if this combination is safe and works well.

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  1. Histologically or cytologically confirmed HR+/HER2- metastatic breast cancer. Participants must have received ≥ 2 prior lines of treatment for metastatic disease, including prior endocrine therapy and CDK4/6 inhibitor in either the adjuvant or advanced/metastatic setting.
  2. Female participants will be required (either continue ongoing or initiate as soon as feasible) to have ovarian function suppression using gonadotropin-releasing hormone (GnRH) agonists (such as goserelin) or be postmenopausal.
  3. Male participants may be required to use GnRH agonists when being treated with fulvestrant at the discretion of the investigator.
  4. Participants must have a stable Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1.
  5. Adequate organ function.
  6. Female participants of childbearing potential and nonsterile male participants with female partners of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study and for 90 days after the last dose of BGB-21447, 3 months after the last dose of BGB-43395, and 2 years after the last dose of fulvestrant.
  7. Food effect substudy only: Participants who are able and willing to fast overnight (≥ 10 hours) and consume a high-fat meal.

Exclusion criteria

  1. Prior Bcl-2 inhibitor exposure.
  2. Known leptomeningeal disease or uncontrolled, untreated brain metastases.
  3. Any malignancy ≤ 3 years before the first dose of study treatment(s) except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent (eg, treated papillary thyroid carcinoma, resected basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast).
  4. Uncontrolled diabetes.
  5. History of hepatitis B or active Hepatitis C infection
  6. China Only: Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers with HBV DNA > 500 IU/ml (or > 2500 copies/ml) at screening.

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

study type

Study type

TREATMENT

phase

Phase

    PHASE1

trial

Study ID

NCT06756932

Intervention or treatment

DRUG: BGB-21447

DRUG: Fulvestrant

DRUG: BGB-43395

Conditions

  • Hormone-receptor-positive Breast Cancer
  • HER2-negative Breast Cancer
  • Metastatic Breast Cancer

  • Condition: Hormone-receptor-positive Breast Cancer, HER2-negative Breast Cancer and more

  • DRUG: BGB-21447 and other drugs

  • Darlinghurst, New South Wales, Australia and more

  • Sponsor: BeiGene

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You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

Are you running this trial?

If you're a clinic or sponsor, you can claim this study

Research sites nearby

Closest Location:

Saint Vincents Hospital Sydney

Select from list below to view details:

  • Saint Vincents Hospital Sydney

    Darlinghurst, New South Wales, Australia

  • Calvary Mater Newcastle

    Waratah, New South Wales, Australia

  • Sunshine Coast University Private Hospital

    Birtinya, Queensland, Australia

  • Peter Maccallum Cancer Centre

    Melbourne, Victoria, Australia

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Who is running the clinical trial?

B

BeiGene

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/ArmIntervention/Treatment
EXPERIMENTAL: Part 1A: BGB-21447 + Fulvestrant
  • Sequential cohorts of increasing dose levels of BGB-21447 will be evaluated in combination with fulvestrant.
Drug: BGB-21447, Drug: Fulvestrant
    EXPERIMENTAL: Part 1B: BGB-21447 + BGB-43395 + Fulvestrant
    • Sequential cohorts of increasing dose levels of BGB-21447 will be evaluated in combination with fulvestrant and BGB-43395.
    Drug: BGB-21447, Drug: Fulvestrant, Drug: BGB-43395
      EXPERIMENTAL: BGB-21447 + Fulvestrant Food Effect Substudy
      • Participants will receive BGB-21447 at the recommended dose with a high-fat meal and under a fasted state in combination with fulvestrant.
      Drug: BGB-21447, Drug: Fulvestrant
        EXPERIMENTAL: Part 2: Dose Expansion, BGB-21447 + Fulvestrant
        • Participants will receive BGB-21447 at the recommended dose(s) for expansion determined in Part 1A in combination with fulvestrant.
        Drug: BGB-21447, Drug: Fulvestrant

          What is the study measuring?

          Primary Outcome

          MeasureDescriptionTime Frame
          Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)Number of participants with AEs and SAEs, including findings from physical examinations, electrocardiograms (ECGs), laboratory assessments, and AEs that meet protocol-defined dose-limiting toxicity criteria.From the first dose of study drug(s) to 30 days after the last dose; up to approximately 6 months
          Recommended Dose for Expansion (RDFE) of BGB-21447 in combination with fulvestrant and in combination with fulvestrant and BGB-43395RDFE of BGB-21447 in combination with fulvestrant and in combination with fulvestrant and BGB-43395 will be determined based upon the maximum tolerated dose (MTD) or maximum administered dose (MAD).Approximately 6 to 9 months

          Secondary Outcome

          MeasureDescriptionTime Frame
          Objective Response Rate (ORR)ORR is defined as the percentage of participants who had confirmed complete response (CR) or partial response (PR) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.Approximately 12 months
          Duration of Response (DOR)DOR is defined as the time from the first determination of an objective response until the first documentation of progression or death, whichever comes first, as assessed by the investigator per RECIST v1.1.Approximately 12 months
          Time to Response (TTR)TTR is defined as the time from the date of the first dose of study drug to the date of the first CR or PR, as assessed by the investigator per RECIST v1.1.Approximately 12 months
          Maximum observed plasma concentration (Cmax) of BGB-21447, BGB-43395, and BGB-43395 metaboliteNot SpecifiedUp to approximately 2 months
          Time to reach maximum observed plasma concentration (Tmax) of BGB-21447, BGB-43395, and BGB-43395 metaboliteNot SpecifiedUp to approximately 2 months
          Area under the concentration-time curve (AUC) of BGB-21447, BGB-43395, and BGB-43395 metaboliteNot SpecifiedUp to approximately 2 months
          Apparent terminal elimination half-life (t1/2) of BGB-21447, BGB-43395, and BGB-43395 metaboliteNot SpecifiedUp to approximately 2 months
          Food Effect Substudy: AUC of BGB-21447 under fasted and fed stateNot SpecifiedUp to approximately 2 months
          Food Effect Substudy: Cmax of BGB-21447 under fasted and fed stateNot SpecifiedUp to approximately 2 months
          Are you running this trial?If you're a clinic or sponsor, you can claim this study.
          Claim this trial

          References

          Clinical Trials Gov: BGB-21447 (Bcl-2 Inhibitor) Combinations for Adults With Hormone-Receptor Positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Metastatic Breast Cancer

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