A Study to Examine the Safety of Different Doses of BG-68501 Given to Participants With Advanced-Stage Tumors

Breast Cancer Clinical Trial

Official title:

A Phase 1a/1b Study of BG-68501, a Selective CDK2 Inhibitor, in Participants With Advanced Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06257264
• Other study ID #: BG-68501-101
• Status: Recruiting
• Phase: Phase 1
• Start date: February 28, 2024
• Est. completion date: December 31, 2026

Study information

• Verified date: April 2024
• Source: BeiGene
• Contact: Study Director
• Phone: 1.877.828.5568
• Email: clinicaltrials[@]beigene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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. The study will also identify a recommended dose for expansion (RDFE) in subsequent disease directed studies. The study will be conducted in 2 parts: Part 1 (dose escalation and safety expansion) and Part 2 (dose expansion).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 108
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

General Inclusion Criteria:

• Female participants with advanced or metastatic HR+/HER2- breast cancer 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.

Part 1 (Dose Escalation) Inclusion Criteria:

• 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, fallopian tube, primary peritoneal cancer (PROC), small cell lung cancer (SCLC), and others.
• Participants should have received prior available systemic therapy for their condition and should be refractory to or intolerant of standard-of-care therapies.
• Participants with advanced solid tumors must have measurable disease per RECIST 1.1.

Part 1 (Safety Expansion) Inclusion Criteria:

• Participants with advanced or metastatic HR+/HER2- breast cancer, PROC, or SCLC.

Part 2 (Dose Expansion) Inclusion Criteria:

• Participants with selected advanced or metastatic HR+/HER2- breast cancer, PROC, SCLC, or advanced solid tumors with a specific gene mutation based on standard-of-care testing.

General Exclusion Criteria:

• Prior therapy selectively targeting CDK2 inhibition. 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, 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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Breast Cancer
• Breast Neoplasms
• Endometrial Cancer
• Endometrial Neoplasms
• Gastric Cancer
• Hormone Receptor Positive HER-2 Negative Breast Cancer
• Ovarian Cancer
• Ovarian Neoplasms
• Prostate Cancer
• Prostatic Neoplasms
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma
• Stomach Neoplasms

Intervention

Drug:
• BG-68501
Planned doses administered orally.
• Fulvestrant
Standard dose administered via intramuscular injection.

Locations

Country	Name	City	State
Australia	Blacktown Cancer and Haematology Centre	Blacktown	New South Wales
Australia	Genesiscare North Shore	St Leonards	New South Wales
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	Titan Health Partners Llc Dba Astera Cancer Care	East Brunswick	New Jersey
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	Number of participants with treatment-emergent AEs and SAEs.	Up to approximately 24 months
Primary	Part 1: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BG-68501	MTD is defined as the highest dose evaluated for which estimated toxicity rate is the closest to the target toxicity rate. MAD is defined as the highest dose administered if MTD is not reached.	Up to approximately 24 months
Primary	Part 1: Recommended dose(s) for Expansion (RDFE) of BG-68501 in participants with solid tumors	RDFE of BG-68501 alone will be determined based upon the MTD or MAD.	Up to approximately 24 months
Primary	Part 1: RDFE of BG-68501 and fulvestrant in participants with hormone-receptor positive (HR+) and human epidermal growth factor 2 negative (HER2-) breast cancer	RDFE of BG-68501 in combination with fulvestrant will be determined based upon the MTD or MAD.	Up to approximately 24 months
Primary	Part 2: Objective Response Rate	ORR is defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR). CR and PR that is confirmed by repeat assessments, as assessed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.	Up to approximately 24 months
Secondary	Part 1: ORR	ORR is defined as the percentage of participants with best overall response of CR or PR. CR and PR that is confirmed by repeat assessments, as assessed by the investigator using RECIST v1.1.	Up to approximately 24 months
Secondary	Part 2: Number of participants with AEs and SAEs	Number of participants with AEs and SAEs, including findings from physical examinations, electrocardiograms (ECGs), and laboratory assessments.	Up to approximately 24 months
Secondary	Parts 1 and 2: Duration of Response (DOR)	DOR is defined as the time from the first confirmed objective response by the investigator using RECIST v1.1 until the first documentation of disease progression after treatment initiation or death, whichever comes first.	Up to approximately 24 months
Secondary	Parts 1 and 2: Time to Response (TTR)	TTR is defined as the time from the treatment initiation to the first determination of overall response by the investigator using RECIST v1.1.	Up to approximately 24 months
Secondary	Parts 1 and 2: Disease Control Rate (DCR)	DCR is defined as the percentage of participants with the best overall response, of a CR, PR, and stable disease assessed by the investigator using RECIST v1.1.	Up to approximately 24 months
Secondary	Parts 1 and 2: Clinical Benefit Rate (CBR)	CBR is defined as the percentage of participants with best overall response of confirmed CR, PR, or stable disease lasting = 24 weeks.	Up to approximately 24 months
Secondary	Part 1: Maximum observed plasma concentration (Cmax) for BG-68501		From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days)
Secondary	Part 1: Observed plasma trough concentration (Ctrough) for BG-68501		From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days)
Secondary	Part 1: Area under the concentration-time curve (AUC) for BG-68501		From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days)
Secondary	Part 1: Half-life (t1/2) for BG-68501		From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days)
Secondary	Part 2: Plasma concentrations for BG-68501		From Cycle 1 Day 1 up to Cycle 5 Day 1 (each cycle is 28 days)