Trial Review

Technical difficulties have been reported by some users of the search function and is being investigated by technical staff. Thank you for your patience and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06120283




Registration number
NCT06120283
Ethics application status
Date submitted
1/11/2023
Date registered
7/11/2023
Date last updated
24/04/2024

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

Experimental: Dose Escalation - Phase 1a: Sequential cohorts of increasing dose levels of BGB-43395 will be evaluated as monotherapy and in combination with either fulvestrant or letrozole.

Experimental: Dose Expansion - Phase 1b: The recommended dose for expansion (RFDE) for BGB-43395 (in combination with fulvestrant) from Phase 1a will be evaluated in HR+ breast cancer and selected tumor 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.
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)
Timepoint [1] 0 0
Up to approximately 3 years
Primary outcome [2] 0 0
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-43395
Timepoint [2] 0 0
Up to approximately 3 years
Primary outcome [3] 0 0
Phase 1a: Recommended Dose for Expansion (RDFE) of BGB-43395
Timepoint [3] 0 0
Up to approximately 3 years
Primary outcome [4] 0 0
Phase 1b: Objective Response Rate (ORR)
Timepoint [4] 0 0
Up to approximately 3 years
Secondary outcome [1] 0 0
Phase 1a: ORR
Timepoint [1] 0 0
Up to approximately 3 years
Secondary outcome [2] 0 0
Phase 1a and 1b: Duration of Response (DOR)
Timepoint [2] 0 0
Up to approximately 3 years
Secondary outcome [3] 0 0
Phase 1a and 1b: Time to Response (TTR)
Timepoint [3] 0 0
Up to approximately 3 years
Secondary outcome [4] 0 0
Phase 1b: Disease Control Rate (DCR)
Timepoint [4] 0 0
Up to approximately 3 years
Secondary outcome [5] 0 0
Phase 1b: Clinical Benefit Rate (CBR)
Timepoint [5] 0 0
Up to approximately 3 years
Secondary outcome [6] 0 0
Phase 1b: Progression-Free Survival (PFS)
Timepoint [6] 0 0
Up to approximately 3 years
Secondary outcome [7] 0 0
Phase 1b: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [7] 0 0
Up to approximately 3 years
Secondary outcome [8] 0 0
Phase 1a: Observed Plasma Maximum Concentration (Cmax) of BGB-43395 and its metabolite
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
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
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
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
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): Participants with histologically or cytologically
confirmed advanced, metastatic, or unresectable solid tumors associated with
dependency on CDK4, including HR+ breast 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.

- Phase 1b (Dose Expansion): 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.

- 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 metastasis.

- Any malignancy = 3 years before the first dose of study drug(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.

- History of hepatitis B or 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
1/05/2026
Actual
Sample size
Target
79
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Blacktown Cancer and Haematology Centre - Blacktown
Recruitment hospital [2] 0 0
Macquarie University - North Ryde
Recruitment hospital [3] 0 0
Austin Health - Heidelberg
Recruitment hospital [4] 0 0
Peter Maccallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2109 - North Ryde
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment postcode(s) [4] 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
North Carolina
Country [3] 0 0
United States of America
State/province [3] 0 0
Ohio
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas

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

Ethics approval
Ethics application status

Summary
Brief summary
This is a dose escalation and dose expansion study to compare how well BGB-43395, a
cyclin-dependent kinase 4 (CDK4) inhibitor, works as monotherapy or in combination with
either fulvestrant or letrozole 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT06120283
Trial related presentations / publications
Public notes

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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT06120283