A Phase 1a/b, Open-label, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BG-C137, an Antibody-Drug Conjugate Targeting FGFR2b, 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
- 168
- 试验地点
- 72
- 主要终点
- Phase 1b: The recommended Phase 2 dose (RP2D) of BG-C137
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of BG-C137 alone and in combination with anticancer agents in participants with advanced solid tumors. The study will be conducted in two phases: Phase 1a (Monotherapy Dose Escalation, and Safety Expansion; Combination Dose Confirmation and Safety Expansion) and Phase 1b (Dose Expansion).
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
- •Histologically or cytologically confirmed advanced or metastatic solid tumors.
- •Life expectancy of ≥ 3 months.
- •Prior standard systemic therapy in the advanced or metastatic setting. Dose Escalation: Participants for whom further standard treatment is not available, not tolerated or determined not appropriate based on the investigator's judgment. Combo Dose Confirmation, Combo Safety Expansion, and Dose Expansion: Participants who have received at least 1 or 2 prior lines of systemic therapy, which included a fluoropyrimidine and/or a platinum in the advanced or metastatic setting
- •Tumors with FGFR2b expression/ or FGFR2 gene amplification. Participants must provide agreement for collection of archival tissue or recently obtained fresh tumor biopsy for central evaluation of FGFR2b expression levels and other biomarker assessments.
- •≥ 1 measurable lesion per RECIST v1.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or
- •Adequate organ function as determined per protocol.
排除标准
- •Prior exposure to topoisomerase I inhibitor (TOP1i)-based antibody-drug conjugate (ADC) therapies or FGFR2b-targeted ADC therapies.
- •Active or chronic corneal disorder, history of corneal transplantation, corneal keratitis, keratoconjunctivitis, keratopathy, corneal abrasion, inflammation or ulceration, other active ocular conditions and any clinically significant corneal disease that prevents adequate monitoring of drug-induced keratopathy.
- •Spinal cord compression, or active leptomeningeal disease or uncontrolled, untreated brain metastasis.
- •Systemic antitumor therapy (including targeted therapy and immunotherapy ≤ 14 days, ≤ 28 days for immuno- oncological antibody, ≤ 14 days or 5 half-lives [whichever is shorter] for chemotherapy, ADCs, or investigational therapy) before first dose of study drug(s).
- •Toxicities due to prior therapy that have not recovered.
- •Any malignancy ≤ 2 years before 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 curatively.
- •History of interstitial lung disease (ILD), noninfectious pneumonitis, oxygen saturation at rest < 92%, or requirement for supplemental oxygen at baseline.
- •Note: Other protocol-defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Phase 1a: Monotherapy Dose Escalation and Safety Expansion
Sequential cohorts of increasing dose levels of BG-C137 will be evaluated as monotherapy
干预措施: BG-C137 (Drug)
Phase 1a: Combination Therapy Dose Confirmation and Safety Expansion
Sequential cohorts will be evaluated to confirm the safety levels of BG-C137 in combination with other anticancer agents at selected dose levels that have been determined to be safe in Monotherapy Dose Escalation
干预措施: Anticancer Agents (Drug)
Phase 1a: Combination Therapy Dose Confirmation and Safety Expansion
Sequential cohorts will be evaluated to confirm the safety levels of BG-C137 in combination with other anticancer agents at selected dose levels that have been determined to be safe in Monotherapy Dose Escalation
干预措施: BG-C137 (Drug)
Phase 1b: Dose Expansion
Recommended Dose(s) of BG-C137 as determined from Ph1a will be evaluated in select indications
干预措施: BG-C137 (Drug)
结局指标
主要结局
Phase 1b: The recommended Phase 2 dose (RP2D) of BG-C137
时间窗: Up to approximately 2 years
The RP2D of BG-C137 monotherapy will be determined based on relevant data, as 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) by Response Evaluations Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BG-C137
时间窗: Up to approximately 2 years
The MTD or MAD is defined as the highest dose evaluated for which the estimated toxicity rate is closest to a target toxicity rate, or the highest dose administered, respectively.
Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Up to approximately 2 years
Number of participants with AEs and SAEs as graded by the National Cancer Institute- Common Terminology Criteria for Adverse Events Version (NCI CTCAE 5.0)), including AEs that meet protocol-defined dose-limiting toxicity (DLT) criteria and AEs meeting protocol-defined adverse event of clinical interest (AECIs)
Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Up to approximately 2 years
Number of participants with AEs and SAEs as graded by the National Cancer Institute- Common Terminology Criteria for Adverse Events Version (NCI CTCAE 5.0)), including AEs that meet protocol-defined dose-limiting toxicity (DLT) criteria and AEs meeting protocol-defined adverse event of clinical interest (AECIs)
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BG-C137
时间窗: Up to approximately 2 years
The MTD or MAD is defined as the highest dose evaluated for which the estimated toxicity rate is closest to a target toxicity rate, or the highest dose administered, respectively.
Phase 1a: Recommended Dose(s) for Expansion (RDFE[s]) of BG-C137 as monotherapy and in combination with anticancer agents
时间窗: Up to approximately 2 years
RDFE(s) is determined based on relevant data, as available
Phase 1b: The recommended Phase 2 dose (RP2D) of BG-C137
时间窗: Up to approximately 2 years
The RP2D of BG-C137 monotherapy will be determined based on relevant data, as 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) by Response Evaluations Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
次要结局
- Phase 1a and 1b: Disease Control Rate (DCR)(Up to approximately 2 years)
- Phase 1a: ORR(Up to approximately 2 years)
- Phase 1a and 1b: Duration of Response (DOR)(Up to approximately 2 years)
- Phase 1b: Progression Free Survival (PFS)(Up to approximately 2 years)
- Phase 1b: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to approximately 2 years)
- Phase 1a: Plasma concentrations of BG-C137 analytes(Up to approximately 1 year; at the end of treatment (maximum of 2 years) and at the first safety follow-up visit (30 days after last dose))
- Phase 1b: Plasma concentrations of BGB-C137 analytes(Up to approximately 1 year; at the end of treatment (maximum of 2 years) and at the first safety follow-up visit (30 days after last dose))
- Phase 1a: Maximum observed plasma concentration (Cmax) of BGB-C137 analytes(Twice in the first 3 months)
- Phase 1a: Time to reach maximum observed plasma concentration (Tmax) of BGB-C137 analytes(Twice in the first 3 months)
- Phase 1a: Minimum Observed Plasma Concentration (Ctrough) Of BGB-C137 analytes(Twice in the first 3 months)
- Phase 1a: Area Under the Plasma Concentration-time Curve (AUC) of BGB-C137 analytes(Twice in the first 3 months)
- Phase 1a: Terminal Half-Life (t1/2) of BGB-C137 analytes(Twice in the first 3 months)
- Phase 1a and 1b: Incidence of Antidrug Antibodies (ADAs) to BGB-C137(Up to approximately 2 years)
- Phase 1a: ORR(Up to approximately 2 years)
- Phase 1a and 1b: Disease Control Rate (DCR)(Up to approximately 2 years)
- Phase 1a and 1b: Duration of Response (DOR)(Up to approximately 2 years)
- Phase 1b: Progression Free Survival (PFS)(Up to approximately 2 years)
- Phase 1b: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to approximately 2 years)
- Phase 1a: Plasma concentrations of BG-C137 analytes(Up to approximately 1 year; at the end of treatment (maximum of 2 years) and at the first safety follow-up visit (30 days after last dose))
- Phase 1b: Plasma concentrations of BGB-C137 analytes(Up to approximately 1 year; at the end of treatment (maximum of 2 years) and at the first safety follow-up visit (30 days after last dose))
- Phase 1a: Maximum observed plasma concentration (Cmax) of BGB-C137 analytes(Twice in the first 3 months)
- Phase 1a: Time to reach maximum observed plasma concentration (Tmax) of BGB-C137 analytes(Twice in the first 3 months)
- Phase 1a: Minimum Observed Plasma Concentration (Ctrough) Of BGB-C137 analytes(Twice in the first 3 months)
- Phase 1a: Area Under the Plasma Concentration-time Curve (AUC) of BGB-C137 analytes(Twice in the first 3 months)
- Phase 1a: Terminal Half-Life (t1/2) of BGB-C137 analytes(Twice in the first 3 months)
- Phase 1a and 1b: Incidence of Antidrug Antibodies (ADAs) to BGB-C137(Up to approximately 2 years)