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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06257264




Registration number
NCT06257264
Ethics application status
Date submitted
5/02/2024
Date registered
13/02/2024
Date last updated
22/11/2024

Titles & IDs
Public title
A Study to Examine the Safety of Different Doses of BG-68501 Given to Participants With Advanced-Stage Tumors
Scientific title
A Phase 1a/1b Study of BG-68501, a Selective CDK2 Inhibitor, in Participants With Advanced Solid Tumors
Secondary ID [1] 0 0
CTR20243059
Secondary ID [2] 0 0
BG-68501-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Small Cell Lung Cancer 0 0
Ovarian Cancer 0 0
Gastric Cancer 0 0
Hormone-receptor-positive Breast Cancer 0 0
Hormone Receptor Positive HER-2 Negative Breast Cancer 0 0
Advanced Solid Tumor 0 0
Endometrial Cancer 0 0
Prostate Cancer 0 0
TNBC - Triple-Negative Breast Cancer 0 0
GastroEsophageal Cancer 0 0
Bladder Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast
Cancer 0 0 0 0
Prostate
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Stomach
Cancer 0 0 0 0
Bladder - transitional cell cancer
Cancer 0 0 0 0
Lung - Small cell
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BG-68501
Treatment: Drugs - Fulvestrant
Treatment: Drugs - BGB-43395

Experimental: Part 1 Part A: Dose Escalation and Safety Expansion (BG-68501 Monotherapy) - Sequential cohorts of increasing dose levels of BG-68501 will be evaluated as monotherapy.

Experimental: Part 1 Part B: Dose Escalation (BG-68501 + Fulvestrant) - Sequential cohorts of increasing dose levels of BG-68501 will be evaluated in combination with fulvestrant.

Experimental: Part 1 Part C: Dose Escalation and Safety Expansion (BG-68501 + Fulvestrant + BGB-43395) - Sequential cohorts of increasing dose levels of BG-68501 will be evaluated in combination with fulvestrant and BGB-43395.

Experimental: Part 2: Dose Expansion - The RFDE for BG-68501 (as monotherapy and in combination with fulvestrant and BGB-43395) from Part 1 will be evaluated in selected tumor cohorts.


Treatment: Drugs: BG-68501
Planned doses administered orally.

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

Treatment: Drugs: BGB-43395
Planned doses administered orally.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [1] 0 0
From the first dose of study drug(s) to 30 days after the last dose; approximately 6-12 months
Primary outcome [2] 0 0
Part 1: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BG-68501
Timepoint [2] 0 0
Up to approximately 24 months
Primary outcome [3] 0 0
Part 1: Recommended dose(s) for Expansion (RDFE) of BG-68501 monotherapy in participants with solid tumors
Timepoint [3] 0 0
Up to approximately 24 months
Primary outcome [4] 0 0
Part 1: RDFE of BG-68501 in combination with fulvestrant and BGB-43395 in participants with HR+/HER2- BC
Timepoint [4] 0 0
Up to approximately 24 months
Primary outcome [5] 0 0
Part 2: Objective Response Rate (ORR)
Timepoint [5] 0 0
Up to approximately 20 months
Secondary outcome [1] 0 0
Part 1: ORR
Timepoint [1] 0 0
Up to approximately 20 months
Secondary outcome [2] 0 0
Part 2: Number of participants with AEs and SAEs
Timepoint [2] 0 0
From the first dose of study drug(s) to 30 days after the last dose; approximately 6-12 months
Secondary outcome [3] 0 0
Parts 1 and 2: Duration of Response (DOR)
Timepoint [3] 0 0
Up to approximately 20 months
Secondary outcome [4] 0 0
Parts 1 and 2: Time to Response (TTR)
Timepoint [4] 0 0
Up to approximately 20 months
Secondary outcome [5] 0 0
Parts 1 and 2: Disease Control Rate (DCR)
Timepoint [5] 0 0
Up to approximately 20 months
Secondary outcome [6] 0 0
Parts 1 and 2: Clinical Benefit Rate (CBR)
Timepoint [6] 0 0
Up to approximately 20 months
Secondary outcome [7] 0 0
Part 1: Maximum observed plasma concentration (Cmax) for BG-68501 and BGB-43395
Timepoint [7] 0 0
2 times in the first 2 months
Secondary outcome [8] 0 0
Part 1: Observed plasma trough concentration (Ctrough) for BG-68501 and BGB-43395
Timepoint [8] 0 0
5 times in the first 2 months
Secondary outcome [9] 0 0
Part 1: Area under the concentration-time curve (AUC) for BG-68501 and BGB-43395
Timepoint [9] 0 0
2 times in the first 2 months
Secondary outcome [10] 0 0
Part 1: Half-life (t1/2) for BG-68501 and BGB-43395
Timepoint [10] 0 0
2 times in the first 2 months
Secondary outcome [11] 0 0
Part 2: Plasma concentrations for BG-68501 and BGB-43395
Timepoint [11] 0 0
5 times in approximately 3 months

Eligibility
Key inclusion criteria
Part 1 (Dose Escalation)

* Monotherapy Cohorts: Participants with histologically or cytologically confirmed advanced or metastatic solid tumors potentially associated with CDK2 dependency including HR+/HER2- breast cancer, platinum refractory or resistant serous ovarian cancer (PROC), endometrial cancer, and others. Prior available standard-of-care systemic therapies for advanced or metastatic disease are required.
* Combination Cohorts (BG-68501 with fulvestrant with or without BGB-43395): Enrollment is restricted to only participants with HR+/HER2- BC. In regions where approved and available, participants must have received one or more lines of treatment for advanced/metastatic disease as well as prior endocrine therapy and a CDK4/6 inhibitor in either the adjuvant or advanced/metastatic setting.

Part 1 (Safety Expansion) and Part 2 (Dose Expansion)

* Participants with advanced, non-resectable, or metastatic HR+/HER2- BC or PROC, including fallopian tube or primary peritoneal cancer.
* PROC participants must have received:

* = 1 line of platinum-containing chemotherapy for advanced disease.
* = 4 prior therapeutic regimens in the advanced/metastatic setting.
* HR+/HER2- BC:

* Participants enrolled in regions where CDK4/6 inhibitors are approved and available must have received = 1 line of therapy including endocrine therapy and a CDK4/6 inhibitor. Participants can have received up to 2 lines of prior cytotoxic chemotherapy or ADC treatments for advanced disease.

General

* Female participants with advanced or metastatic HR+/HER2- BC will be required to have ovarian function suppression using gonadotropin hormone-releasing hormone (GnRH) agonists (such as goserelin) or be postmenopausal.
* Eastern Cooperative Oncology Group (ECOG) Performance Status = 1.
* Adequate organ function.
* For dose escalation, participants with advanced solid tumors other than HR+/HER2- BC must have measurable disease per RECIST 1.1. Participants with HR+/HER2- BC with bone-only disease are eligible for dose escalation only. For safety expansion and dose expansion, all participants must have =1 measurable lesion per RECIST v 1.1.

General
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* For all cohorts: Prior therapy selectively targeting CDK2 inhibition.
* For triple combination cohorts: Prior therapy targeting CDK2 or 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. Participants with a history of treated central nervous system (CNS) metastases may be eligible if they meet additional criteria.
* 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, treated papillary thyroid carcinoma, or carcinoma in situ of the cervix or breast).
* Uncontrolled diabetes.
* Infection requiring systemic antibacterial, antifungal, or antiviral therapy 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.
* Any major surgical procedure = 28 days before the first dose of study treatment(s).
* 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
11/03/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
28/02/2028
Actual
Sample size
Target
138
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
Genesiscare North Shore - St Leonards
Recruitment hospital [3] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [4] 0 0
Cancer Research South Australia - Adelaide
Recruitment hospital [5] 0 0
Monash Health - Clayton
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
4102 - Brisbane
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Missouri
Country [3] 0 0
United States of America
State/province [3] 0 0
New Jersey
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
China
State/province [5] 0 0
Beijing
Country [6] 0 0
China
State/province [6] 0 0
Guangdong

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

Ethics approval
Ethics application status

Summary
Brief summary
This study is a first-in-human (FIH), Phase 1a/1b study of BG-68501, a cyclin-dependent kinase-2 inhibitor (CDK2i), to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of BG-68501 in participants with advanced, nonresectable, or metastatic solid tumors as monotherapy and in combination with fulvestrant with or without BGB-43395, a selective CDK4 inhibitor, in adults with hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer (BC). The study will also identify a recommended dose for expansion (RDFE) for BG-68501 as monotherapy and in combination for subsequent disease directed studies.

The study will be conducted in 2 parts: Part 1 (dose escalation and safety expansion) and Part 2 (dose expansion).
Trial website
https://clinicaltrials.gov/study/NCT06257264
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
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06257264