A Multicenter Open-Label Phase 1a/1b Study to Evaluate the Safety and Preliminary Antitumor Activity of BGB-R046 as Monotherapy and in Combination With Tislelizumab in Participants With Selected Advanced or Metastatic Solid Tumors
概览
- 阶段
- 1 期
- 干预措施
- BGB-R046
- 疾病 / 适应症
- Solid Tumor
- 发起方
- BeOne Medicines
- 入组人数
- 75
- 试验地点
- 10
- 主要终点
- Phase 1a: Number of Participant with Adverse Events, Serious Adverse Events, Adverse Events of Clinical Interest and Dose-limiting Toxicities
- 状态
- 进行中（未招募）
- 最后更新
- 上个月
概览
简要总结
This is a first-in-human (FIH) study that will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of BGB-R046 as a single agent and in combination with tislelizumab (BGB-A317) in participants with advanced or metastatic immune-sensitive solid tumors.
详细描述
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 able to provide a signed and dated written informed consent prior to any study-specific procedures, sampling, or data collection
- •Participants with histologically or cytologically confirmed advanced, metastatic, and unresectable solid tumors who have previously received standard systemic therapy or for whom standard treatment is not available, not tolerated, or determined not appropriate based on the investigator's judgement
- •≥ 1 measurable lesion per RECIST v1.1
- •Able to provide an archived tumor tissue sample
- •Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
- •Adequate organ function
- •Life expectancy \>12 weeks as determined by the investigator
排除标准
- •Active leptomeningeal disease or uncontrolled, untreated brain metastasis
- •Active autoimmune diseases or history of autoimmune diseases that may relapse
- •Any malignancy ≤ 3 years before the first dose of study drug(s) except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast)
- •Any condition that required systemic treatment with either corticosteroids (\> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before the first dose of study drug(s)
- •History of interstitial lung disease, noninfectious pneumonitis (including immune mediated), or uncontrolled lung diseases including pulmonary fibrosis, or acute lung diseases.
- •Experienced ≥ Grade 3 imAE(s) on prior immuno-oncology agent (anti-PD-1, anti CTLA4, or other experimental drugs)
- •Uncontrolled diabetes \> Grade 1 laboratory test abnormalities in potassium, sodium, or corrected calcium despite standard medical management, or ≥ Grade 3 hypoalbuminemia ≤ 14 days before the first dose of study drug(s).
- •Infection (including tuberculosis infection, or other) requiring systemic (oral or intravenous) antibacterial, antifungal, or antiviral therapy ≤ 14 days before the first dose of study drug(s)
- •Immunodeficiency as assessed by the investigator to be not suitable for treatment with immune modulating anticancer agents
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Phase 1a: Part A: Dose Escalation Monotherapy
Sequential cohorts of increasing dose levels of BGB R046 will be evaluated as monotherapy.
干预措施: BGB-R046
Phase 1a: Part B: Dose Escalation Combination Therapy
Sequential cohorts of increasing dose levels of BGB R046 will be evaluated in combination with tislelizumab.
干预措施: BGB-R046
Phase 1a: Part B: Dose Escalation Combination Therapy
Sequential cohorts of increasing dose levels of BGB R046 will be evaluated in combination with tislelizumab.
干预措施: Tislelizumab
Phase 1b: Dose Expansion and Dose Optimization
The recommended dose(s) for expansion (RDFE) for BGB-R046 in combination with tislelizumab from Phase 1a will be evaluated in selected indications.
干预措施: BGB-R046
Phase 1b: Dose Expansion and Dose Optimization
The recommended dose(s) for expansion (RDFE) for BGB-R046 in combination with tislelizumab from Phase 1a will be evaluated in selected indications.
干预措施: Tislelizumab
结局指标
主要结局
Phase 1a: Number of Participant with Adverse Events, Serious Adverse Events, Adverse Events of Clinical Interest and Dose-limiting Toxicities
时间窗: Up to approximately 2 years
Number of participants with AEs including serious adverse events (SAEs), defined as any unfavorable and unintended sign (including abnormal laboratory findings), symptom, or disease temporally associated with the use of study drugs, whether considered related to study drugs or not as graded by the National Cancer Institute-Common Terminology Criteria for Adverse Events \[NCI CTCAE) V5.0/American Society for Transplantation and Cellular Therapy (ASTCT) for cytokine release syndrome \[CRS\] and immune effector cell associated neurotoxicity syndrome \[ICANS\])
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-R046
时间窗: Up to approximately 2 years
MTD is defined as the highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 30% or the highest dose administered, respectively
Phase 1a: Recommended Dose(s) for Expansion (RDFE[s]) of BGB-R046
时间窗: Up to approximately 2 years
The potential RDFE\[s\] of BGB-R046 administered as monotherapy and in combination with tislelizumab will be determined based on the totality of the data and will also take in consideration the long term tolerability, pharmacokinetics, preliminary antitumor activity and any other relevant data available
Phase 1b: Overall Response Rate (ORR)
时间窗: Up to approximately 2 years
ORR is defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) as determined by investigators per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
次要结局
- Phase 1a and Phase 1b: Duration of Response (DOR)(Up to approximately 2 years)
- Phase 1a: ORR(Up to approximately 2 years)
- Phase 1a: Time to Response (TTR)(Up to approximately 2 years)
- Phase 1a: Clinical Benefit Rate (CBR)(Up to approximately 2 years)
- Phase 1a and Phase 1b: Disease Control Rate (DCR)(Up to approximately 2 years)
- Phase 1b: Progression-free survival (PFS)(Up to approximately 2 years)
- Phase 1a and 1b: Minimum Observed Plasma Concentration (Ctrough) Of BGB-R046(Cycle 1 and Cycle 5 (each cycle is 21 days))
- Phase 1a and 1b: Area Under the Plasma Concentration-time Curve (AUC) of BGB-R046(Cycle 1 and Cycle 5 (each cycle is 21 days))
- Phase 1b: Number of Participants with Adverse Events (AEs)(Up to approximately 2 years)
- Phase 1a: Plasma concentrations of BGB-R046 analytes(Predose and at select time points in Cycles 1, 2 and 5; predose at select Cycles between Cycles 3 and 25 (each cycle is 21 days); and at the first safety follow-up visit (conducted 30 days after the last dose of study drug))
- Phase 1b: Plasma concentrations of BGB-R046 analytes(Predose and after end of infusion in Cycles 1 and 5; predose at select Cycles between Cycles 1 and 25 (each cycle is 21 days); and at the first safety follow-up visit (conducted 30 days after the last dose of study drug))
- Phase 1b: Plasma concentrations of tislelizumab(Predose and after end of infusion in Cycles 1 and 5; predose at select Cycles between Cycles 1 and 17 (each cycle is 21 days); and at the first safety follow-up visit (conducted 30 days after the last dose of study drug))
- Phase 1a and 1b: Maximum observed plasma concentration (Cmax) of BGB-R046(Cycle 1 and Cycle 5 (each cycle is 21 days))
- Phase 1a and 1b: Terminal Half-Life (t1/2) of BGB-R046(Cycle 1 and Cycle 5 (each cycle is 21 days))
- Phase 1a and 1b: Incidence of Antidrug Antibodies (ADAs) to BGB-R046 and tislelizumab(Periodic sampling up to Cycle 25 (each cycle is 21 days) and at the first safety follow up visit up to approximately 2 years (conducted 30 days after the last dose of study drug))