Advanced Solid Tumor
Conditions
Keywords
advanced solid tumor, BGB-58067, MTAP deficiency, BG-89894
Brief summary
This is an open-label, multicenter, first-in-human dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of BGB-58067 alone, in combination with BG-89894, and in combination with standard of care therapy in participants with advanced solid tumors and with methylthioadenosine phosphorylase (MTAP) deficiency.
Detailed description
BGB-58067 is a new drug designed to target a specific protein called protein arginine methyltransferase 5 (PRMT5). This protein is involved in many cell activities and can promote cancer growth when it is overactive. High levels of PRMT5 are linked to poor outcomes in several types of cancer. This new study will check how safe and helpful a potential anticancer drug called BGB-58067 is. This drug will be tested alone, in combination with BG-89894, and in combination with standard of care therapy in participants with advanced solid tumors and with MTAP deficiency. Note: Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.
Interventions
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 sign the ICF and be capable of giving written informed consent * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 or Karnofsky Performance Scale (KPS) ≥ 70 * Life expectancy ≥ 3 months * Evidence of homozygous loss of MTAP or lost MTAP expression in the tumor tissue * Able to provide tumor sample to meet the minimum tissue requirement for central MTAP deficiency testing * Participants with histologically or cytologically confirmed advanced, metastatic, or unresectable solid tumors, whose diseases have progressed or recurred after receiving standard systemic therapy or radiotherapy, or for whom standard systemic therapy is not available or tolerated, or would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard treatment in the opinion of the investigator; participants with advanced, metastatic, or unresectable solid tumors who have not received prior systemic treatment or have received one cycle of standard-of-care therapies will be enrolled in selected cohorts * Adequate organ function
Exclusion criteria
* Prior treatment with any methylthioadenosine (MTA)-cooperative PRMT5 inhibitor or methionine adenosyltransferase 2a (MAT2A) inhibitor * Active leptomeningeal disease or symptomatic spinal cord compression * Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage * Any malignancy ≤ 2 years before first dose of study drug except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively * Significantly impaired pulmonary function * Clinically significant infections * Serologically active hepatitis B or C infection * Known HIV infection. Participants with treated HIV infection may be included in Phase 1b if they meet certain criteria * High cardiovascular risk factors * QTcF \> 470 ms based on the screening triplicate 12-lead ECG records and/or a history of additional risk factors for torsade de pointes (eg, heart failure, hypokalemia, or a family history of Long QT Syndrome) * Toxicities (because of prior anticancer therapy) that have not recovered to baseline or stabilized * Participants who are unable to swallow or with disease/procedure significantly affecting gastrointestinal function * Female participants who are pregnant or are breastfeeding * Concurrent participation in another therapeutic clinical study (participation in observational or noninterventional studies is allowed) Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1a: Number of Participants with Adverse Events and Serious Adverse Events | From first dose of the study drug(s) to 30 days after the last dose or initiation of a new anticancer therapy, whichever occurs first (approximately 13 months) | Number of participants with AEs and SAEs, including findings from physical examinations, electrocardiograms (ECGs), and laboratory assessments. |
| Phase 1a: Number of Participants with Adverse Events that meet Dose-Limiting Toxicity (DLT) criteria | Approximately 1 month | — |
| Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-58067 alone, in combination with BG-89894, and in combination with standard of care therapy | Approximately 1 month | 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. |
| Phase 1a: Recommended Dose(s) for Expansion (RDFE[s]) of BGB-58067 alone, in combination with BG-89894, and in combination with standard of care therapy | Approximately 13 months | RDFE of BGB-58067 alone, in combination with BG-89894, and in combination with standard of care therapy will be determined based upon the MTD or MAD. |
| Phase 1b: Recommended Phase 2 Dose (RP2D) of BGB-58067 alone, in combination with BG-89894, and in combination with standard of care therapy | Approximately 2 years | RP2D established from Phase 1a for BGB-58067 alone, in combination with BG-89894, and in combination with standard of care therapy for administration in selected tumor types. |
| Phase 1b: Objective Response Rate (ORR) | Approximately 2 years | ORR is defined as the percentage of participants with confirmed complete response (CR) or partial response (PR), as assessed by the investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1a: Objective Response Rate (ORR) | Approximately 2 years | ORR is defined as the percentage of participants with confirmed CR or PR, as assessed by the investigator. |
| Phase 1a and 1b: Maximum observed plasma concentration (Cmax) of BGB-58067 | Approximately 2 months | — |
| Phase 1a and 1b: Minimum observed plasma concentration (Cmin) of BGB-58067 | Approximately 9 months | — |
| Phase 1a and 1b: Time to reach maximum observed plasma concentration (Tmax) of BGB-58067 | Approximately 2 months | — |
| Phase 1a and 1b: Apparent oral clearance (CL/F) for BGB-58067 | Approximately 2 months | — |
| Phase 1a and 1b: Half-life (t1/2) of BGB-58067 | Approximately 2 months | — |
| Phase 1a and 1b: Area under the concentration-time curve (AUC) of BGB-58067 | Approximately 2 months | — |
| Phase 1a and 1b: Apparent volume of distribution (Vz/F) for BGB-58067 | Approximately 2 months | — |
| Phase 1a and 1b: Accumulation ratio (AR) for BGB-58067 | Approximately 2 months | — |
| Phase 1a and 1b: Plasma concentrations of BGB-58067 | Approximately 9 months | — |
| Phase 1a and 1b: Duration of Response (DOR) | Approximately 2 years | DOR is defined as the time from the first determination of an objective response until first documentation of progression or death, whichever occurs first, as assessed by the investigator. |
| Phase 1a and 1b: Disease Control Rate (DCR) | Approximately 2 years | DCR is defined as the percentage of participants with best overall response of a CR, PR, and stable disease, as assessed by the investigator. |
| Phase 1b: Number of Participants with AEs and SAEs | From first dose of the study drug(s) to 30 days after the last dose or initiation of a new anticancer therapy, whichever occurs first (approximately 13 months) | Number of participants with AEs and SAEs, including findings from physical examinations, electrocardiograms (ECGs), and laboratory assessments. |
| Phase 1b: Progression-Free Survival (PFS) | Approximately 2 years | PFS is defined as the time from the date of the first dose of study drug to the date of first documentation of progressive disease assessed by investigator or death, whichever occurs first, as assessed by the investigator. |
Countries
Australia, China, Denmark, France, South Korea, Spain, United States
Contacts
CONTACTStudy Director
STUDY_DIRECTORStudy Director
BeOne Medicines
Outcome results
None listed