A Phase 1 Study Investigating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of BG-T187, an EGFR×MET Trispecific Antibody, Alone and in Combination With Other Therapeutic Agents in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 153
- 试验地点
- 47
- 主要终点
- Phase 1b: Recommended Phase 2 dose (RP2D) of BG-T187 alone and in combination with other therapeutic agents
研究概览
简要总结
This is a first-in-human (FIH), Phase 1a/1b, open-label, multicenter, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of BG-T187 alone and in combination with other therapeutic agents in participants with advanced 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to provide a signed and dated written informed consent prior to any study-specific procedures, sampling, or data collection.
- •Participants must be ≥ 18 years of age or the legal age of consent in the jurisdiction in which the study is taking place.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status ≤
- •Participants with selected histologically or cytologically confirmed advanced, metastatic, and unresectable solid tumors who have been previously treated, including but not limited to non-small cell lung cancer (NSCLC), colorectal cancer (CRC).
- •≥ 1 measurable or nonmeasurable lesion as assessed by RECIST v1.
- •for Phase 1a Part A; ≥ 1 measurable lesion per RECIST v1.
- •for Phase 1a Part B and Phase 1b.
- •Adequate organ function.
排除标准
- •Prior severe allergic reactions or hypersensitivity to the active ingredient and excipients of BG-T187 or other monoclonal antibodies.
- •Spinal cord compression, active leptomeningeal disease, or uncontrolled, untreated brain metastasis.
- •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).
- •History of interstitial lung disease (ILD) or noninfectious pneumonitis requiring steroids or other immune suppressive agents ≤ 2 years before the first dose of the study drug, or with current ILD/noninfectious pneumonitis, or where suspected ILD/noninfectious pneumonitis cannot be ruled out by imaging during screening.
- •Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage (recurrence ≤14 days after intervention).
- •Active hepatitis C.
- •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).
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Phase 1a: Part A: Monotherapy Dose Escalation with Intravenous Administration
Sequential cohorts of increasing dose levels of BG-T187 will be evaluated as monotherapy.
干预措施: Drug: BG-T187 (Drug)
Phase 1a: Part B: Monotherapy Dose Escalation with Subcutaneous Administration
Sequential cohorts of increasing dose levels of BG-T187 will be evaluated as monotherapy.
干预措施: Drug: BG-T187 (Drug)
Phase 1b: Combination Therapy: BG-T187 + Other Therapeutic Agents
Participants will receive BG-T187 in combination with Other Therapeutic Agents.
干预措施: Other Therapeutic Agents (Drug)
Phase 1a Part C: Safety Expansion
BG-T187 dose levels that have been determined to be safe and tolerable in Part B will be investigated.
干预措施: Drug: BG-T187 (Drug)
Phase 1b: Monotherapy Dose Expansion with Subcutaneous Administration
Participants will receive BG-T187 monotherapy at the recommended dose(s) for expansion (RDFE) determined in Phase 1a.
干预措施: Drug: BG-T187 (Drug)
Phase 1b: Combination Therapy: BG-T187 + Other Therapeutic Agents
Participants will receive BG-T187 in combination with Other Therapeutic Agents.
干预措施: Drug: BG-T187 (Drug)
结局指标
主要结局
Phase 1b: Recommended Phase 2 dose (RP2D) of BG-T187 alone and in combination with other therapeutic agents
时间窗: Approximately 2 years
R2PD is determined based on safety, tolerability, PK, preliminary antitumor activity, and other relevant data, as available
Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: 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 \[ICANS\]); and adverse events meeting protocol-defined dose-limiting toxicity (DLT) criteria
Phase 1a: Recommended Dose(s) for Expansion (RDFE[s]) of BG-T187
时间窗: Approximately 2 years
RDFE(s) is determined based on the MAD or MTD, taking into consideration the long-term tolerability, pharmacokinetics (PK), preliminary antitumor activity, and any other relevant data, as available
Phase 1b: Overall Response Rate (ORR)
时间窗: Approximately 2 years
ORR is defined as the percentage of participants with confirmed best overall response (BOR) complete response (CR) or partial response (PR) as determined by investigators per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: 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 \[ICANS\]); and adverse events meeting protocol-defined dose-limiting toxicity (DLT) criteria
Phase 1a: Maximum Administered Dose (MAD) or Maximum Tolerated Dose (MTD) of BG-T187
时间窗: Approximately 2 years
MTD or MAD 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 BG-T187
时间窗: Approximately 2 years
RDFE(s) is determined based on the MAD or MTD, taking into consideration the long-term tolerability, pharmacokinetics (PK), preliminary antitumor activity, and any other relevant data, as available
Phase 1b: Overall Response Rate (ORR)
时间窗: Approximately 2 years
ORR is defined as the percentage of participants with confirmed best overall response (BOR) complete response (CR) or partial response (PR) as determined by investigators per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Phase 1b: Recommended Phase 2 dose (RP2D) of BG-T187 alone and in combination with other therapeutic agents
时间窗: Approximately 2 years
R2PD is determined based on safety, tolerability, PK, preliminary antitumor activity, and other relevant data, as available
次要结局
- Phase 1b: Number of Participants with AEs and SAEs(Approximately 2 years)
- Phase 1a: ORR(Approximately 2 years)
- Phase 1a and 1b: Duration of Response (DOR)(Approximately 2 years)
- Phase 1b: Progression Free Survival (PFS)(Approximately 2 years)
- Phase 1a: Time to maximum plasma concentration (Tmax) of BG-T187(From Cycle 1 to Cycle 3 (each cycle is 28 days))
- Phase 1a: Terminal Half-Life (t1/2) of BG-T187(From Cycle 1 to Cycle 3 (each cycle is 28 days))
- Phase 1a: ORR(Approximately 2 years)
- Phase 1a and 1b: Duration of Response (DOR)(Approximately 2 years)
- Phase 1a and 1b: Disease Control Rate (DCR)(Approximately 2 years)
- Phase 1b: Progression Free Survival (PFS)(Approximately 2 years)
- Phase 1a: Maximum observed plasma concentration (Cmax) of BG-T187(From Cycle 1 to Cycle 3 (each cycle is 28 days))
- Phase 1a: Area Under the Plasma Concentration-time Curve (AUC) of BG-T187(From Cycle 1 to Cycle 3 (each cycle is 28 days))
- Phase 1b: Number of Participants with AEs and SAEs(Approximately 2 years)
- Phase 1a and 1b: Number of participants with anti-drug antibodies (ADAs) to BG-T187(From Cycle 1 Day 1 up to 30 days after last dose (approximately 2 years))