A Phase 1a/b Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of PRMT5 Inhibitor BGB-58067 Alone and in Combination With Anticancer Agents in Patients With Advanced Solid Tumors
概览
- 阶段
- 1 期
- 干预措施
- BGB-58067
- 疾病 / 适应症
- Advanced Solid Tumor
- 发起方
- BeOne Medicines
- 入组人数
- 244
- 试验地点
- 95
- 主要终点
- Phase 1a: Number of Participants with Adverse Events and Serious Adverse Events
- 状态
- 招募中
- 最后更新
- 上个月
概览
简要总结
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.
详细描述
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.
研究者
入排标准
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
Phase 1a: BGB-58067 Monotherapy Dose Escalation and Safety Expansion
Sequential cohorts of increasing dose levels of BGB-58067 as monotherapy will be evaluated.
干预措施: BGB-58067
Phase 1a: BGB-58067 + BG-89894 Combination Therapy Dose Escalation
Sequential cohorts of increasing dose levels of BGB-58067 in combination with BGB-89894 will be evaluated.
干预措施: BGB-58067
Phase 1a: BGB-58067 + BG-89894 Combination Therapy Dose Escalation
Sequential cohorts of increasing dose levels of BGB-58067 in combination with BGB-89894 will be evaluated.
干预措施: BG-89894
Phase 1a: BGB-58067 + Standard of Care Combination Therapy Dose Escalation
Sequential cohorts of increasing dose levels of BGB-58067 in combination with standard of care therapy will be evaluated.
干预措施: BGB-58067
Phase 1a: BGB-58067 + Standard of Care Combination Therapy Dose Escalation
Sequential cohorts of increasing dose levels of BGB-58067 in combination with standard of care therapy will be evaluated.
干预措施: Standard of Care Therapy
Phase 1b: Dose Expansion and Optimization
Recommended Dose(s) for Expansion (RDFE\[s\]) of BGB-58067 alone, in combination with BG-89894, and in combination with standard of care therapy will be evaluated for selected indications and regimen(s) based on emerging data.
干预措施: BGB-58067
Phase 1b: Dose Expansion and Optimization
Recommended Dose(s) for Expansion (RDFE\[s\]) of BGB-58067 alone, in combination with BG-89894, and in combination with standard of care therapy will be evaluated for selected indications and regimen(s) based on emerging data.
干预措施: BG-89894
Phase 1b: Dose Expansion and Optimization
Recommended Dose(s) for Expansion (RDFE\[s\]) of BGB-58067 alone, in combination with BG-89894, and in combination with standard of care therapy will be evaluated for selected indications and regimen(s) based on emerging data.
干预措施: Standard of Care Therapy
结局指标
主要结局
Phase 1a: Number of Participants with Adverse Events and Serious Adverse Events
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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)
时间窗: 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.
次要结局
- Phase 1a: Objective Response Rate (ORR)(Approximately 2 years)
- 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)
- Phase 1a and 1b: Disease Control Rate (DCR)(Approximately 2 years)
- 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))
- Phase 1b: Progression-Free Survival (PFS)(Approximately 2 years)