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

Phase 1RecruitingNCT07226349

BeOne Medicines105 enrolled

Overview

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.

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

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

105

Conditions

Advanced Solid Tumor

Interventions

BG-75098DRUG

Administered orally.

BGB-43395DRUG

Administered orally.

FulvestrantDRUG

Administered by intramuscular injection.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (5)

Icon Cancer Centre Wesley

Auchenflower, Queensland, Australia

RECRUITING

Cabrini Hospital Malvern

Malvern East, Victoria, Australia

RECRUITING

Peter Maccallum Cancer Centre

Melbourne, Victoria, Australia

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Up to approximately 2 years

Secondary Outcomes

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.

Time frame: Up to approximately 2 years

Phase 1a: Duration of Response (DOR) as Assessed by the Investigator

Central Contacts

Study Director

CONTACT

8778285568 clinicaltrials@beonemed.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Sun Yat Sen Memorial Hospital, Sun Yat Sen University (South)

Guangzhou, Guangdong, China

RECRUITING

Rigshospitalet

Copenhagen, Denmark

RECRUITING

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.

Time frame: 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.

Time frame: 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.

Time frame: Up to approximately 2 years

Phase 1b: DOR as Assessed by the Investigator

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Up to approximately 2 years

Phase 1b: PFS

Time frame: 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.

Time frame: Up to approximately 2 years

Observed Plasma Maximum Concentration (Cmax) of BG-75098

Time frame: Assessed at select time points between Cycle 1 and Cycle 2 (each Cycle is 28 days)

Observed Plasma Trough Concentration (Ctrough) of BG-75098

Time frame: 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

Time frame: Assessed at select time points between Cycle 1 and Cycle 2 (each Cycle is 28 days)

Terminal Half-Life (t1/2) of BG-75098

Time frame: Assessed at select time points between Cycle 1 and Cycle 2 (each Cycle is 28 days)

Phase 1b: Plasma Concentrations of BG-75098

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Assessed at select time points between Cycle 1 and Cycle 2 (each Cycle is 28 days)

Plasma Concentrations of BGB-43395

Time frame: Assessed at select time points between Cycle 1 and Cycle 7 (each Cycle is 28 days)