A Study of BG-75098 Alone and in Combination With Other Agents in Adults With Advanced Solid Tumors

A Phase 1a/1b, Open-Label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BG-75098 Alone and in Combination With Other Agents in Patients With Advanced Solid Tumors

The purpose of this study is to evaluate safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of BG-75098 alone and in combination with BGB-43395 and fulvestrant in participants with advanced solid tumors.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: BGB-43395; Drug: BG-75098; Drug: Fulvestrant

Detailed Description

This study will be conducted in 2 phases: Phase 1a Dose Escalation and Phase 1b Dose Expansion.

• Study Type: Interventional
• Enrollment (Estimated): 105
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Study Director; Phone Number: 8778285568; Email: clinicaltrials@beonemed.com

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, NSW 2148
      • Recruiting
      • Blacktown Cancer and Haematology Centre
    • St Leonards, New South Wales, Australia, NSW 2065
      • Recruiting
      • GenesisCare St Leonards
  • Queensland
    • Auchenflower, Queensland, Australia, QLD 4066
      • Recruiting
      • Icon Cancer Centre Wesley
  • Victoria
    • Malvern, Victoria, Australia, VIC 3144
      • Recruiting
      • Cabrini Hospital Malvern
    • Melbourne, Victoria, Australia, VIC 3000
      • Recruiting
      • Peter MacCallum Cancer Centre
  • Western Australia
    • Nedlands, Western Australia, Australia, WA 6009
      • Recruiting
      • One Clinical Research
• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100021
      • Recruiting
      • Cancer Hospital Chinese Academy of Medical Sciences
  • Guangdong
    • Guangzhou, Guangdong, China, 510245
      • Recruiting
      • Sun Yat Sen Memorial Hospital, Sun Yat Sen University (South)
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Recruiting
      • Harbin Medical University Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Recruiting
      • Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
    • Wuhan, Hubei, China, 430048
      • Recruiting
      • Union Hospital Tongji Medical College Huazhong University of Science and Technologyjinyinhu Branch
  • Jiangsu
    • Nanjing, Jiangsu, China, 210036
      • Recruiting
      • Jiangsu Province Hospital Longjiang Branch
  • Shandong
    • Jinan, Shandong, China, 250000
      • Recruiting
      • Qilu Hospital of Shandong University
    • Weifang, Shandong, China, 261000
      • Recruiting
      • Weifang Peoples Hospital
• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Rigshospitalet
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-0004
      • Recruiting
      • University of Alabama At Birmingham Hospital
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Sidney Kimmel Comprehensive Cancer At Johns Hopkins
  • Texas
    • Houston, Texas, United States, 77030-4009
      • Recruiting
      • The University of Texas MD Anderson Cancer Center
    • Houston, Texas, United States, 77054
      • Recruiting
      • NEXT Houston
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226-1222
      • Recruiting
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participants must have measurable disease as assessed by RECIST v1.1.
• Participants must have a stable Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Participants must have adequate organ function.
• Dose Escalation Part A: Participants with histologically or cytologically confirmed advanced, metastatic, or unresectable solid tumors potentially associated with cyclin-dependent kinase 2 (CDK2) dependency. Participants should have received prior treatment with available standard-of-care (SOC) systemic therapies for advanced/metastatic disease, or for whom standard therapy is not available or not tolerated.
• Dose Escalation Part B: Patients with histologically or cytologically confirmed advanced, metastatic, or unresectable solid tumors who have received ≥ 1 prior line of systemic therapy in the metastatic setting.
• Dose Expansion Cohort 1: Participants with histologically or cytologically confirmed advanced, metastatic, or unresectable CDK4/6 inhibitor-progressed solid tumors.
• Dose Expansion Cohort 2: Participants with advanced solid tumors. Participants with primary platinum refractory disease are not eligible. Participants should have received ≥ 1 line of platinum-containing chemotherapy and ≤ 4 prior therapeutic regimens in the advanced/metastatic setting.

Exclusion Criteria:

• For all cohorts: Prior therapy selectively targeting CDK2 inhibition or degradation.
• For combination cohorts: Prior therapy selectively targeting CDK4. Prior CDK4/6 inhibitor standard of care therapy is permitted and required in local regions where it is approved and available.
• Participants with active leptomeningeal disease or uncontrolled, untreated brain metastasis.

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1a, Part A: Dose Escalation, BG-75098 Monotherapy; Sequential cohorts of increasing dose levels of BG-75098 will be evaluated as monotherapy.	Drug: BG-75098; Administered orally.
Experimental: Phase 1a, Part B: Dose Escalation, BG-75098 Combination; Sequential cohorts of increasing dose levels of BG-75098 will be evaluated in combination with BGB-43395 and fulvestrant.	Drug: BGB-43395; Administered orally.; Drug: BG-75098; Administered orally.; Drug: Fulvestrant; Administered by intramuscular injection.
Experimental: Phase 1b, Cohort 1: Dose Expansion, BG-75098 Combination; Participants will receive BG-75098 at the recommended dose level from Phase 1a in combination with BGB-43395 and fulvestrant.	Drug: BGB-43395; Administered orally.; Drug: BG-75098; Administered orally.; Drug: Fulvestrant; Administered by intramuscular injection.
Experimental: Phase 1b, Cohort 2: Dose Expansion, BG-75098 Monotherapy; Participants will receive BG-75098 as monotherapy at the recommended dose level from Phase 1a.	Drug: BG-75098; Administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1a: Number of Participants with Adverse Events (AEs)	Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including physical examination findings, electrocardiogram results, laboratory values, and AEs meeting protocol-defined dose-limiting toxicity (DLT) criteria.	From first dose to 30 days after last dose, up to approximately 12 months
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BG-75098	MTD is determined based on a target for dose-limiting toxicities. MAD is defined as the maximum administered dose, and it is used when MTD is not reached.	Up to approximately 2 years
Phase 1a: Recommended Dose(s) for Expansion (RDFE[s]) of BG-75098 as Monotherapy and in Combination with BGB-43395 and Fulvestrant	The RDFE(s) will be determined from safety, tolerability, pharmacokinetic, pharmacodynamic biomarker(s), preliminary antitumor activity, and any other relevant data that are obtained from the dose escalation phase.	Up to approximately 2 years
Phase 1b: Objective Response Rate (ORR) as Assessed by the Investigator	ORR is defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR), as assessed by the investigator using RECIST v1.1.	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1a: ORR as Assessed by the Investigator	ORR is defined as the percentage of participants with best overall response of CR or PR, as assessed by the investigator using RECIST v1.1.	Up to approximately 2 years
Phase 1a: Duration of Response (DOR) as Assessed by the Investigator	DOR is defined as the time from the first confirmed objective response assessed 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 2 years
Phase 1a: Time to Response (TTR) as Assessed by the Investigator	TTR is defined as the time from treatment initiation to the first determination of overall response assessed by the investigator using RECIST v1.1.	Up to approximately 2 years
Phase 1a: Progression-Free Survival (PFS) as Assessed by the Investigator	PFS is defined as the time from the date of the first dose of study treatment to the date of the first documentation of progressive disease assessed by the investigator using RECIST v1.1 or death, whichever occurs first.	Up to approximately 2 years
Phase 1b: DOR as Assessed by the Investigator	DOR is defined as the time from the first confirmed objective response assessed 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 2 years
Phase 1b: TTR as Assessed by the Investigator	TTR is defined as the time from treatment initiation to the first determination of overall response assessed by the investigator using RECIST v1.1.	Up to approximately 2 years
Phase 1b: Disease Control Rate (DCR)	DCR is defined as the percentage of participants with a best overall response, of CR, PR, or stable disease assessed by the investigator using RECIST v1.1.	Up to approximately 2 years
Phase 1b: 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 2 years
Phase 1b: PFS	PFS is defined as the time from the date of the first dose of study treatment to the date of the first documentation of progressive disease assessed by the investigator using RECIST v1.1 or death, whichever occurs first.	Up to approximately 2 years
Phase 1b: Number of Participants with AEs	Number of participants with TEAEs and SAEs, including physical examination findings, electrocardiogram results, and laboratory values.	Up to approximately 2 years
Observed Plasma Maximum Concentration (Cmax) of BG-75098		Assessed at select time points between Cycle 1 and Cycle 2 (each Cycle is 28 days)
Observed Plasma Trough Concentration (Ctrough) of BG-75098		Assessed at select time points between Cycle 1 and Cycle 2 (each Cycle is 28 days)
Area Under the Concentration-Time Curve (AUC) of BG-75098		Assessed at select time points between Cycle 1 and Cycle 2 (each Cycle is 28 days)
Terminal Half-Life (t1/2) of BG-75098		Assessed at select time points between Cycle 1 and Cycle 2 (each Cycle is 28 days)
Phase 1b: Plasma Concentrations of BG-75098		Assessed at select time points between Cycle 1 and Cycle 7 (each Cycle is 28 days)
Phase 1a: Observed Plasma Maximum Concentration (Cmax) of BGB-43395		Assessed at select time points between Cycle 1 and Cycle 2 (each Cycle is 28 days)
Phase 1a: Observed Plasma Trough Concentration (Ctrough) of BGB-43395		Assessed at select time points between Cycle 1 and Cycle 2 (each Cycle is 28 days)
Phase 1a: Area Under the Concentration-Time Curve (AUC) of BGB-43395		Assessed at select time points between Cycle 1 and Cycle 2 (each Cycle is 28 days)
Phase 1a: Terminal Half-Life (t1/2) of BGB-43395		Assessed at select time points between Cycle 1 and Cycle 2 (each Cycle is 28 days)
Plasma Concentrations of BGB-43395		Assessed at select time points between Cycle 1 and Cycle 7 (each Cycle is 28 days)

Collaborators and Investigators

• Sponsor: BeOne Medicines
• Investigators: Study Director: Study Director, BeOne Medicines

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2025
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: November 6, 2025
• First Submitted That Met QC Criteria: November 6, 2025
• First Posted (Actual): November 10, 2025

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: CDK4; CDK2; CDK4 inhibitor; Cyclin-Dependent Kinase 2- Targeted Protein Degrader
• Additional Relevant MeSH Terms: 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-75098-101; 2025-523165-19-00 (Ctis)

Plan for Individual participant data (IPD)

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

IPD Plan Description

BeOne 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.

BeOne 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 BeOne 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