BGB-43395 Alone or as Part of Combination Therapies in Participants With Breast Cancer and Other Advanced Solid Tumors

NCT06120283
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Phase
Phase 1
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Recruitment status
Recruiting
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Participants
433
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Lead sponsor
BeOne Medicines
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Start date
2023-12-01
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Number of sites
62
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Summary
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 or in combination with fulvestrant, letrozole, or elacestrant in participants with hormone receptor positive (HR+) and human epidermal growth factor 2 negative (HER2-) breast cancer (BC) and other advanced solid tumors. The main purpose of this study is to explore the recommended dosing for BGB-43395.
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Short title
BGB-43395 Alone or as Part of Combination Therapies in Participants With Breast Cancer and Other Advanced Solid Tumors
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Official title
A Phase 1a/1b Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of the CDK4 Inhibitor BGB-43395, Alone or as Part of Combination Therapies in Patients With Metastatic HR+/HER2- Breast Cancer and Other Advanced Solid Tumors
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1
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Study type
Interventional
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Completion date
2029-12-01
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First posted
2023-11-07
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Registry last updated
2026-08-28
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Primary completion date
2029-12-01
clinicaltrials.gov
Start date
2023-12-01
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Participants
433
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Participant count basis
Estimated
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Planned participants
433
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Protocol amendments
4
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Number of sites
62
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
BeOne Medicines
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06120283
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ClinicalTrials.gov ID
NCT06120283
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Registry record
Open registry record
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Allocation
Not randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Timeframe: Up to approximately 60 months

    Number of participants with AEs and SAEs, including findings from physical examinations, electrocardiograms (ECGs), laboratory assessments, and that meet protocol-defined dose-limiting toxicity (DLT) criteria.

  2. Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-43395

    Timeframe: Up to approximately 60 months

    MTD is defined as the highest dose evaluated for which estimated toxicity rate is the closest to the target toxicity rate of 28%. MAD is defined as the highest dose administered if MTD is not reached.

  3. Phase 1a: Recommended Dose for Expansion (RDFE) of BGB-43395

    Timeframe: Up to approximately 60 months

    RDFE of BGB-43395 alone or in combination with fulvestrant, letrozole, or elacestrant will be determined based upon the MTD or MAD.

  4. Phase 1b: Objective Response Rate (ORR)

    Timeframe: Up to approximately 60 months

    ORR is defined as the percentage of participants who have confirmed complete response (CR) or partial response (PR) assessed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

  1. Phase 1a: ORR

    Timeframe: Up to approximately 60 months

    ORR is defined as the percentage of participants who have confirmed CR or PR assessed by the investigator using RECIST v1.1.

  2. Phase 1a and 1b: Duration of Response (DOR)

    Timeframe: Up to approximately 60 months

    DOR is defined as the time from the first determination of an overall response per RECIST v1.1 until the first documentation of disease progression or death, whichever occurs first as assessed by the investigator.

  3. Phase 1a and 1b: Time to Response (TTR)

    Timeframe: Up to approximately 60 months

    TTR is defined as the time from the date of the first dose of study drugs to the date of the first determination of objective response by the investigator using RECIST v1.1.

  4. Phase 1b: Disease Control Rate (DCR)

    Timeframe: Up to approximately 60 months

    DCR is defined as the percentage of participants with best overall response of CR, PR, or stable disease assessed by the investigator using RECIST v1.1.

  5. Phase 1b: Clinical Benefit Rate (CBR)

    Timeframe: Up to approximately 60 months

    CBR is defined as the percentage of participants with best overall response of confirmed CR, PR, or stable disease lasting ≥ 24 weeks.

  6. Phase 1b: Progression-Free Survival (PFS)

    Timeframe: Up to approximately 60 months

    PFS is defined as the time from the date of the first dose of study drug(s) to the date of the first documentation of progressive disease assessed by the investigator using RECIST v1.1 or death, whichever occurs first.

  7. Phase 1b: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Timeframe: Up to approximately 60 months

    Number of participants with AEs and SAEs, including findings from physical examinations, electrocardiograms (ECGs), and laboratory assessments.

  8. Phase 1a: Observed Plasma Maximum Concentration (Cmax) of BGB-43395 and its metabolite

    Timeframe: From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days)

  9. Phase 1a: Observed Plasma Trough Concentration (Ctrough) of BGB-43395 and its metabolite

    Timeframe: From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days)

  10. Phase 1a: Area under the concentration-time curve (AUC) of BGB-43395 and its metabolite

    Timeframe: From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days)

  11. Phase 1a: Half-life (t1/2) of BGB-43395 and its metabolite

    Timeframe: From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days)

  12. Phase 1b: Plasma concentrations of BGB-43395 and its metabolite

    Timeframe: From Cycle 1 Day 1 up to Cycle 5 Day 1 (each cycle is 28 days)

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • Phase 1a (Dose Escalation): Participants with histologically or cytologically confirmed advanced, metastatic, or unresectable solid tumors associated with dependency on CDK4, including HR+ breast cancer, ovarian cancer, endometrial cancer, non-small cell lung cancer, and others. For combination with elacestrant, participants must have received at least 1 prior line of treatment for advanced/metastatic disease including prior endocrine therapy and CDK4/6 inhibitor in either the adjuvant or advanced/metastatic setting.
  • Phase 1a Safety Expansion: For combination with fulvestrant in regions where approved and available, participants with HR+ breast cancer must have received at least 1 prior line of treatment including endocrine therapy and a CDK4/6 inhibitor. For combination with letrozole, participants must be CDK4/6 inhibitor treatment naïve and have not received any previous systemic treatment for advanced disease.
  • Phase 1b: Participants with HR+/HER2- breast cancer.
  • Phase 1b: For combination with fulvestrant, participants with HR+/HER2- breast cancer enrolled in regions where CDK4/6 inhibitors are approved and available must have received 1-2 lines of therapy for advanced/metastatic disease including endocrine therapy and a CDK4/6 inhibitor. Participants can have received up to 2 lines of prior cytotoxic chemotherapy for advanced disease. For combination cohorts with letrozole, participants must be CDK4/6 inhibitor treatment naïve and have not received any previous systemic treatment for advanced disease.
  • Stable Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
  • Female participants with metastatic HR+/HER2- breast cancer must be postmenopausal or receiving ovarian function suppression treatment.
  • Adequate organ function without symptomatic visceral disease.

  • Known leptomeningeal disease or uncontrolled, untreated brain metastases.
  • 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, resected basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast).
  • Uncontrolled diabetes.
  • Infection requiring systemic antibacterial, antifungal, or antiviral therapy ≤ 28 days before the first dose of study drug(s), or symptomatic COVID-19 infection.
  • Participants with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers with HBV DNA ≥ 500 IU/mL (or ≥ 2500 copies/mL) at screening.
  • Participants with active hepatitis C infection.
  • Prior allogeneic stem cell transplantation, or organ transplantation.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Sources for eligibility
clinicaltrials.gov

  • Sarah Cannon Research Institute (Scri) At Health OneDenver, United StatesRecruiting
  • Florida Cancer Specialists and Research InstituteLake Mary, United StatesCompleted
  • Karmanos Cancer InstituteDetroit, United StatesCompleted
  • Washington University School of MedicineSt Louis, United StatesRecruiting
  • Duke Cancer CenterDurham, United StatesRecruiting
  • James Cancer Hospital and Solove Research InstituteColumbus, United StatesRecruiting
  • Scri Oncology PartnersNashville, United StatesRecruiting
  • The University of Texas Md Anderson Cancer CenterHouston, United StatesRecruiting
  • Next DallasIrving, United StatesRecruiting
  • Next OncologySan Antonio, United StatesRecruiting
  • Blacktown Cancer and Haematology CentreBlacktown, AustraliaRecruiting
  • Southern Highlands Private HospitalBowral, AustraliaRecruiting
  • Concord Repatriation General HospitalConcord, AustraliaRecruiting
  • Macquarie UniversityNorth Ryde, AustraliaRecruiting
  • Townsville University HospitalDouglas, AustraliaRecruiting
  • Genesiscare St AndrewsAdelaide, AustraliaRecruiting
  • Austin HealthHeidelberg, AustraliaCompleted
  • Peter Maccallum Cancer CentreMelbourne, AustraliaRecruiting
  • Fundacao Pio Xii Hospital de Amor de BarretosBarretos, BrazilRecruiting
  • Hospital Sirio Libanes BrasiliaBrasília, BrazilRecruiting
  • Centro de Pesquisas Oncologicas CeponFlorianópolis, BrazilRecruiting
  • Liga Norte Riograndene Contra O CancerNatal, BrazilRecruiting
  • Fundacao Universidade de Caxias Do Sul Instituto de Pesquisas Em SaudePetrópolis, BrazilRecruiting
  • Hospital Sao Lucas Da Pucrs Uniao Brasileira de Educacao E AssistenciaPorto Algre, BrazilRecruiting
  • Instituto Nacional de CancerRio de Janeiro, BrazilRecruiting

And 37 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2023
  • 2023-506888-34-00
  • CTR20243370
Sources for references
clinicaltrials.gov

Related records

Drugs (4)

Lead sponsors (1)

Conditions (3)

Targets (2)