Advanced Solid Tumor
Conditions
Keywords
Cyclin-Dependent Kinase 2- Targeted Protein Degrader, CDK2, CDK4, CDK4 inhibitor
Brief summary
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.
Detailed description
This study will be conducted in 2 phases: Phase 1a Dose Escalation and Phase 1b Dose Expansion.
Interventions
DRUGBG-75098
Administered orally.
DRUGBGB-43395
Administered orally.
DRUGFulvestrant
Administered by intramuscular injection.
Sponsors
BeOne Medicines
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1a: Number of Participants with Adverse Events (AEs) | From first dose to 30 days after last dose, up to approximately 12 months | 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. |
| Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BG-75098 | Up to approximately 2 years | 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. |
| Phase 1a: Recommended Dose(s) for Expansion (RDFE[s]) of BG-75098 as Monotherapy and in Combination with BGB-43395 and Fulvestrant | Up to approximately 2 years | 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. |
| Phase 1b: Objective Response Rate (ORR) as Assessed by the Investigator | Up to approximately 2 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1a: ORR as Assessed by the Investigator | Up to approximately 2 years | 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. |
| Phase 1a: Duration of Response (DOR) as Assessed by the Investigator | Up to approximately 2 years | 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. |
| Phase 1a: Time to Response (TTR) as Assessed by the Investigator | Up to approximately 2 years | TTR is defined as the time from treatment initiation to the first determination of overall response assessed by the investigator using RECIST v1.1. |
| Phase 1a: Progression-Free Survival (PFS) as Assessed by the Investigator | Up to approximately 2 years | 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. |
| Phase 1b: DOR as Assessed by the Investigator | Up to approximately 2 years | 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. |
| Phase 1b: TTR as Assessed by the Investigator | Up to approximately 2 years | TTR is defined as the time from treatment initiation to the first determination of overall response assessed by the investigator using RECIST v1.1. |
| Phase 1b: Disease Control Rate (DCR) | Up to approximately 2 years | 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. |
| Phase 1b: Clinical Benefit Rate (CBR) | Up to approximately 2 years | CBR is defined as the percentage of participants with best overall response of confirmed CR, PR, or stable disease lasting ≥ 24 weeks. |
| Phase 1b: PFS | Up to approximately 2 years | 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. |
| Phase 1b: Number of Participants with AEs | Up to approximately 2 years | Number of participants with TEAEs and SAEs, including physical examination findings, electrocardiogram results, and laboratory values. |
| 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) | — |
Countries
Australia, China, Denmark, United States
Contacts
CONTACTStudy Director
STUDY_DIRECTORStudy Director
BeOne Medicines
Outcome results
None listed