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

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

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, including evaluation of food effect) and Part 2 (dose expansion).

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer; Small Cell Lung Cancer; Gastric Cancer; Ovarian Cancer; Prostate Cancer; Bladder Cancer; Advanced Solid Tumor; Endometrial Cancer; GastroEsophageal Cancer; TNBC - Triple-Negative Breast Cancer; Hormone Receptor Positive HER-2 Negative Breast Cancer; Hormone-receptor-positive Breast Cancer
• Intervention / Treatment: Drug: BGB-43395; Drug: Fulvestrant; Drug: BG-68501

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, NSW 2148
      • Blacktown Cancer and Haematology Centre
    • Darlinghurst, New South Wales, Australia, NSW 2010
      • Saint Vincents Hospital Sydney
    • Kingswood, New South Wales, Australia, NSW 2747
      • Nepean Hospital
    • St Leonards, New South Wales, Australia, NSW 2065
      • Genesiscare North Shore
  • Queensland
    • Woolloongabba, Queensland, Australia, QLD 4102
      • Princess Alexandra Hospital
  • South Australia
    • Adelaide, South Australia, Australia, SA 5000
      • Cancer Research South Australia
  • Victoria
    • Clayton, Victoria, Australia, VIC 3168
      • Monash Health
• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Beijing Cancer Hospital
    • Beijing, Beijing Municipality, China, 100021
      • Cancer Hospital Chinese Academy of Medical Sciences
  • Guangdong
    • Guangzhou, Guangdong, China, 510245
      • Sun Yat Sen Memorial Hospital, Sun Yat Sen University (South)
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Harbin Medical University Cancer Hospital
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital
  • Liaoning
    • Shenyang, Liaoning, China, 110022
      • Shengjing Hospital of China Medical Universityhuaxiang Branch
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • The First Affiliated Hospital of Xian Jiaotong University
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Center
  • Jerusalem, Israel, 9103102
    • Shaare Zedek Medical Center
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital
• United States
  • California
    • Newport Beach, California, United States, 92663-4162
      • Hoag Memorial Presbyterian
  • Florida
    • Lake Mary, Florida, United States, 32746-2115
      • Florida Cancer Specialists and Research Institute
  • Missouri
    • St Louis, Missouri, United States, 63110-1010
      • Washington University School of Medicine
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816-4096
      • Titan Health Partners Llc Dba Astera Cancer Care
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105-2108
      • Avera Cancer Institute
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Part 1 (Dose Escalation) Inclusion Criteria:

• 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. The requirements for enrollment into a food effect evaluation cohort are the same as the monotherapy cohorts with the exception that participants with gastric cancer and gastroesophageal adenocarcinoma are excluded.
• 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. If applicable, the requirements for enrollment into a food effect evaluation cohort are the same as the combination cohorts.

Part 1 (Safety Expansion) and Part 2 (Dose Expansion) Inclusion Criteria:

• 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 Inclusion Criteria:

• 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 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.
• Active hepatitis B infection 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: BG-68501; Planned doses administered orally.
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.	Drug: Fulvestrant; Standard dose administered via intramuscular injection.; Other Names: Faslodex®; Drug: BG-68501; Planned doses administered orally.
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.	Drug: BGB-43395; Planned doses administered orally.; Drug: Fulvestrant; Standard dose administered via intramuscular injection.; Other Names: Faslodex®; Drug: BG-68501; Planned doses administered orally.
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.	Drug: BGB-43395; Planned doses administered orally.; Drug: Fulvestrant; Standard dose administered via intramuscular injection.; Other Names: Faslodex®; Drug: BG-68501; Planned doses administered orally.
Experimental: Part 1: Food Effect Evaluation; Participants will receive BG-68501 at a dose level that is determined safe and tolerable to evaluate food effect. Food effect may also be evaluated for BG-68501 in combination with fulvestrant.	Drug: Fulvestrant; Standard dose administered via intramuscular injection.; Other Names: Faslodex®; Drug: BG-68501; Planned doses administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Part 1: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	Number of participants with treatment-emergent AEs and SAEs.	From the first dose of study drug(s) to 30 days after the last dose; approximately 6-12 months
Part 1: Recommended dose(s) for Expansion (RDFE) of BG-68501 monotherapy in participants with solid tumors	RDFE of BG-68501 alone will be determined based upon the MTD or MAD.	Up to approximately 24 months
Part 1: RDFE of BG-68501 in combination with fulvestrant and BGB-43395 in participants with HR+/HER2- BC	RDFE of BG-68501 in combination with fulvestrant and BGB-43395 will be determined based upon the MTD or MAD.	Up to approximately 24 months
Part 2: Objective Response Rate (ORR)	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 20 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 20 months
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.	From the first dose of study drug(s) to 30 days after the last dose; approximately 6-12 months
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 20 months
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 20 months
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 20 months
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 assessed by the investigator using RECIST v1.1.	Up to approximately 20 months
Part 1: Maximum observed plasma concentration (Cmax) for BG-68501 and BGB-43395		2 times in the first 2 months
Part 1: Observed plasma trough concentration (Ctrough) for BG-68501 and BGB-43395		5 times in the first 2 months
Part 1: Area under the concentration-time curve (AUC) for BG-68501 and BGB-43395		2 times in the first 2 months
Part 1: Half-life (t1/2) for BG-68501 and BGB-43395		2 times in the first 2 months
Part 2: Plasma concentrations for BG-68501 and BGB-43395		5 times in approximately 3 months

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Study Director: Study Director, BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2024
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: February 5, 2024
• First Submitted That Met QC Criteria: February 5, 2024
• First Posted (Actual): February 13, 2024

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: breast cancer; endometrial cancer; prostate cancer; bladder cancer; ovarian cancer; gastric cancer; urothelial cancer; small cell lung cancer; gastroesophageal cancer; fulvestrant; BGB-43395; cdk2 inhibitor; BG-68501; HR+ HER2- breast cancer; cdk4 inhibitor
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Uterine Diseases; Genital Diseases, Female; Lung Diseases; Endocrine Gland Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Skin Diseases; Breast Diseases; Urologic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Uterine Neoplasms; Urinary Bladder Diseases; Skin and Connective Tissue Diseases; Prostatic Neoplasms; Stomach Neoplasms; Ovarian Neoplasms; Breast Neoplasms; Small Cell Lung Carcinoma; Urinary Bladder Neoplasms; Triple Negative Breast Neoplasms; Endometrial Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Fulvestrant
• Other Study ID Numbers: BG-68501-101; CTR20243059 (Registry Identifier: ChinaDrugTrials.org); 2024-517324-19-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

BeiGene shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

BeiGene shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeiGene review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No