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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06120283




Registration number
NCT06120283
Ethics application status
Date submitted
1/11/2023
Date registered
7/11/2023
Date last updated
11/07/2025

Titles & IDs
Public title
BGB-43395 Alone or as Part of Combination Therapies in Participants With Breast Cancer and Other Advanced Solid Tumors
Scientific 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
Secondary ID [1] 0 0
2023-506888-34-00
Secondary ID [2] 0 0
BGB-43395-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumor 0 0
Advanced Breast Cancer 0 0
Metastatic Breast Cancer 0 0
Hormone-receptor-positive Breast Cancer 0 0
Hormone Receptor Positive Breast Carcinoma 0 0
Hormone Receptor Positive Malignant Neoplasm of Breast 0 0
HER2-negative Breast Cancer 0 0
Hormone Receptor Positive HER-2 Negative Breast Cancer 0 0
Non-small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast
Cancer 0 0 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BGB-43395
Treatment: Drugs - Fulvestrant
Treatment: Drugs - Letrozole
Treatment: Drugs - Elacestrant

Experimental: Dose Escalation and Safety Expansion - 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.

Experimental: Dose Expansion - 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.


Treatment: Drugs: BGB-43395
Planned doses administered orally.

Treatment: Drugs: Fulvestrant
Standard dose administered via intramuscular injection.

Treatment: Drugs: Letrozole
Standard dose administered orally as a tablet.

Treatment: Drugs: Elacestrant
Standard dose administered orally as a tablet.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
Up to approximately 60 months
Primary outcome [2] 0 0
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-43395
Assessment method [2] 0 0
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.
Timepoint [2] 0 0
Up to approximately 60 months
Primary outcome [3] 0 0
Phase 1a: Recommended Dose for Expansion (RDFE) of BGB-43395
Assessment method [3] 0 0
RDFE of BGB-43395 alone or in combination with fulvestrant, letrozole, or elacestrant will be determined based upon the MTD or MAD.
Timepoint [3] 0 0
Up to approximately 60 months
Primary outcome [4] 0 0
Phase 1b: Objective Response Rate (ORR)
Assessment method [4] 0 0
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.
Timepoint [4] 0 0
Up to approximately 60 months
Secondary outcome [1] 0 0
Phase 1a: ORR
Assessment method [1] 0 0
ORR is defined as the percentage of participants who have confirmed CR or PR assessed by the investigator using RECIST v1.1.
Timepoint [1] 0 0
Up to approximately 60 months
Secondary outcome [2] 0 0
Phase 1a and 1b: Duration of Response (DOR)
Assessment method [2] 0 0
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.
Timepoint [2] 0 0
Up to approximately 60 months
Secondary outcome [3] 0 0
Phase 1a and 1b: Time to Response (TTR)
Assessment method [3] 0 0
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.
Timepoint [3] 0 0
Up to approximately 60 months
Secondary outcome [4] 0 0
Phase 1b: Disease Control Rate (DCR)
Assessment method [4] 0 0
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.
Timepoint [4] 0 0
Up to approximately 60 months
Secondary outcome [5] 0 0
Phase 1b: Clinical Benefit Rate (CBR)
Assessment method [5] 0 0
CBR is defined as the percentage of participants with best overall response of confirmed CR, PR, or stable disease lasting = 24 weeks.
Timepoint [5] 0 0
Up to approximately 60 months
Secondary outcome [6] 0 0
Phase 1b: Progression-Free Survival (PFS)
Assessment method [6] 0 0
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.
Timepoint [6] 0 0
Up to approximately 60 months
Secondary outcome [7] 0 0
Phase 1b: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Assessment method [7] 0 0
Number of participants with AEs and SAEs, including findings from physical examinations, electrocardiograms (ECGs), and laboratory assessments.
Timepoint [7] 0 0
Up to approximately 60 months
Secondary outcome [8] 0 0
Phase 1a: Observed Plasma Maximum Concentration (Cmax) of BGB-43395 and its metabolite
Assessment method [8] 0 0
Timepoint [8] 0 0
From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days)
Secondary outcome [9] 0 0
Phase 1a: Observed Plasma Trough Concentration (Ctrough) of BGB-43395 and its metabolite
Assessment method [9] 0 0
Timepoint [9] 0 0
From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days)
Secondary outcome [10] 0 0
Phase 1a: Area under the concentration-time curve (AUC) of BGB-43395 and its metabolite
Assessment method [10] 0 0
Timepoint [10] 0 0
From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days)
Secondary outcome [11] 0 0
Phase 1a: Half-life (t1/2) of BGB-43395 and its metabolite
Assessment method [11] 0 0
Timepoint [11] 0 0
From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days)
Secondary outcome [12] 0 0
Phase 1b: Plasma concentrations of BGB-43395 and its metabolite
Assessment method [12] 0 0
Timepoint [12] 0 0
From Cycle 1 Day 1 up to Cycle 5 Day 1 (each cycle is 28 days)

Eligibility
Key inclusion criteria
* Phase 1a (Dose Escalation) and 1b (Dose Expansion): 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.
* Phase 1a: Received prior therapy for their condition (if available) and should be refractory to, or intolerant of standard-of-care therapies. In regions where approved and available, participants with HR+ breast cancer must have received at least 2 prior lines of treatment including endocrine therapy and a CDK4/6 inhibitor. 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 1b: Selected tumor cohorts will include HR+/HER2- breast cancer and additional tumor types.
* Phase 1b: Participants with HR+/HER2- breast cancer enrolled in regions where CDK4/6 inhibitors are approved and available must have received at least one line of therapy for advanced disease including endocrine therapy and a CDK4/6 inhibitor. Participants can have received up to 2 lines of prior cytotoxic chemotherapy 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior therapy selectively targeting CDK4 (prior CDK4/6 inhibitor therapy is permitted and required in local regions where it is approved and available).
* 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/06/2028
Actual
Sample size
Target
300
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Blacktown Cancer and Haematology Centre - Blacktown
Recruitment hospital [2] 0 0
Southern Highlands Private Hospital - Bowral
Recruitment hospital [3] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [4] 0 0
Macquarie University - North Ryde
Recruitment hospital [5] 0 0
Townsville University Hospital - Douglas
Recruitment hospital [6] 0 0
Genesiscare St Andrews - Adelaide
Recruitment hospital [7] 0 0
Austin Health - Heidelberg
Recruitment hospital [8] 0 0
Peter Maccallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2576 - Bowral
Recruitment postcode(s) [3] 0 0
2139 - Concord
Recruitment postcode(s) [4] 0 0
2109 - North Ryde
Recruitment postcode(s) [5] 0 0
4814 - Douglas
Recruitment postcode(s) [6] 0 0
5000 - Adelaide
Recruitment postcode(s) [7] 0 0
3084 - Heidelberg
Recruitment postcode(s) [8] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Michigan
Country [4] 0 0
United States of America
State/province [4] 0 0
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
Brazil
State/province [9] 0 0
Barretos
Country [10] 0 0
Brazil
State/province [10] 0 0
Brasilia
Country [11] 0 0
Brazil
State/province [11] 0 0
Florianopolis
Country [12] 0 0
Brazil
State/province [12] 0 0
Natal
Country [13] 0 0
Brazil
State/province [13] 0 0
Petropolis
Country [14] 0 0
Brazil
State/province [14] 0 0
Porto Algre
Country [15] 0 0
Brazil
State/province [15] 0 0
Rio de Janeiro
Country [16] 0 0
Brazil
State/province [16] 0 0
Salvador
Country [17] 0 0
Brazil
State/province [17] 0 0
Sao Paulo
Country [18] 0 0
China
State/province [18] 0 0
Beijing
Country [19] 0 0
China
State/province [19] 0 0
Fujian
Country [20] 0 0
China
State/province [20] 0 0
Guangdong
Country [21] 0 0
China
State/province [21] 0 0
Heilongjiang
Country [22] 0 0
China
State/province [22] 0 0
Jiangxi
Country [23] 0 0
China
State/province [23] 0 0
Liaoning
Country [24] 0 0
China
State/province [24] 0 0
Shanghai
Country [25] 0 0
France
State/province [25] 0 0
Bordeaux
Country [26] 0 0
France
State/province [26] 0 0
Caen
Country [27] 0 0
France
State/province [27] 0 0
Lille
Country [28] 0 0
France
State/province [28] 0 0
Marseille
Country [29] 0 0
France
State/province [29] 0 0
Paris
Country [30] 0 0
France
State/province [30] 0 0
Rennes
Country [31] 0 0
France
State/province [31] 0 0
St Herblain
Country [32] 0 0
France
State/province [32] 0 0
Villejuif
Country [33] 0 0
Japan
State/province [33] 0 0
Aichi
Country [34] 0 0
Japan
State/province [34] 0 0
Chiba
Country [35] 0 0
Japan
State/province [35] 0 0
Shizuoka
Country [36] 0 0
Korea, Republic of
State/province [36] 0 0
Gyeonggi-do
Country [37] 0 0
Korea, Republic of
State/province [37] 0 0
Incheon Gwang'yeogsi
Country [38] 0 0
Korea, Republic of
State/province [38] 0 0
Seoul Teugbyeolsi
Country [39] 0 0
Malaysia
State/province [39] 0 0
Georgetown
Country [40] 0 0
Malaysia
State/province [40] 0 0
Kuala Lumpur
Country [41] 0 0
Malaysia
State/province [41] 0 0
Kuching
Country [42] 0 0
Malaysia
State/province [42] 0 0
Putrajaya
Country [43] 0 0
Moldova, Republic of
State/province [43] 0 0
Chisinau
Country [44] 0 0
New Zealand
State/province [44] 0 0
Auckland
Country [45] 0 0
New Zealand
State/province [45] 0 0
Christchurch
Country [46] 0 0
Thailand
State/province [46] 0 0
Muang

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
BeiGene
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
BeiGene
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Study Director
Address 0 0
Country 0 0
Phone 0 0
1.877.828.5568
Email 0 0
clinicaltrials@beigene.com
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT06120283