Phase 1a/1b, Open-Label Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of a CDAC Degrading EGFR, BG-60366, in Patients With EGFR-Mutant Non-Small Cell Lung Cancer
概览
- 阶段
- 1 期
- 干预措施
- BG-60366
- 疾病 / 适应症
- Non-Small Cell Lung Cancer
- 发起方
- BeOne Medicines
- 入组人数
- 33
- 试验地点
- 65
- 主要终点
- Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
- 状态
- 进行中（未招募）
- 最后更新
- 17天前
概览
简要总结
This is an open-label, multicenter, Phase 1a/1b clinical study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of BG-60366, a highly potent, selective EGFR-mutation targeted Chimeric Degradation Activation Compound (CDAC). BG-60366 is designed to degrade mutant EGFR, which is a common cause for Non-Small Cell Lung Cancer (NSCLC). This study will evaluate how well BG-60366 works in participants with advanced or metastatic EGFR-mutant NSCLC.
The study will be conducted in 2 parts: 1) Phase 1a Dose Escalation and Safety Expansion, and 2) 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.
研究者
入排标准
入选标准
- •Histologically or cytologically confirmed diagnosis of NSCLC, carrying an EGFR activating mutation prior to receiving standard EGFR-tyrosine kinase inhibitor (EGFR-TKI)
- •Phase 1a general inclusion criteria:
- •Disease progression on prior third-generation EGFR-TKI for advanced or metastatic disease, and either progressed or ineligible for currently available standard-of-care treatment (eg, platinum-based chemotherapy) after EGFR-TKI treatment
- •Phase 1a safety expansion
- •Documentation of EGFR resistance mutations (ie, C797s)
- •At least ≥ 1 evaluable lesion (for Phase 1a Dose Escalation) or at least ≥ 1 measurable lesion (for Phase 1a Safety Expansion or Phase 1b Dose Expansion) per RECIST v1.1
- •EGFR resistance mutations may be detected locally either from tumor tissue or circulating tumor DNA (ctDNA) in blood, and samples used for detection of resistance mutations must be collected after progression on the most recent systemic antitumor treatment
- •Adequate organ function
- •Stable Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1
排除标准
- •Any previous histologic or cytologic evidence of small cell or combined small cell/non-small cell disease in the archival tumor tissue or tumor biopsy before enrollment
- •Symptomatic spinal cord compression
- •Brain metastases which are symptomatic and/or requiring emergency treatment (eg, starting steroid, or stereotactic radiation/whole-brain radiation within 2 weeks before first dose of study drug)
- •Prior treatment with fourth-generation EGFR-TKI, other CDAC/proteolysis-targeting chimeras (PROTAC) compounds targeting EGFR mutations, or other drugs with the mechanism of action specifically targeting EGFR resistance mutations (eg, C797X) (except for the first- to third-generation EGFR-TKIs)
- •Any history of interstitial lung disease (ILD) or ≥ Grade 2 noninfectious pneumonitis ≤ 2 years before the first dose of study drug, or has current ILD/noninfectious pneumonitis, or where suspected active ILD/noninfectious pneumonitis cannot be ruled out by imaging during screening
- •Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Phase 1a: Dose Escalation and Safety Expansion
Sequential cohorts of increasing dose levels of BG-60366 will be evaluated as monotherapy.
干预措施: BG-60366
Phase 1b: Dose Expansion
Recommended Dose(s) for Expansion (RDFE\[s\]) of BG-60366 as monotherapy determined from Phase 1a will be evaluated.
干预措施: BG-60366
结局指标
主要结局
Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From first dose of the study drug to 30 days after the last dose or initiation of a new anticancer therapy, whichever occurs first (approximately 18 months)
Number of participants with AEs and SAEs, including findings from laboratory assessments, electrocardiograms (ECGs), and physical examinations, and that meet protocol-defined dose-limiting toxicity (DLT) criteria.
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD)
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) of BG-60366
时间窗: Approximately 18 months
RDFE of BG-60366 will be determined based upon the MTD or MAD.
Phase 1b: Number of Participants with Adverse Events and Serious Adverse Events
时间窗: From first dose of the study drug to 30 days after the last dose or initiation of a new anticancer therapy, whichever occurs first (approximately 24 months)
Number of participants with AEs and SAEs, including findings from physical examinations, ECGs, and laboratory assessments as needed.
Phase 1b: Overall Response Rate (ORR)
时间窗: Approximately 24 months
ORR is defined as the percentage of participants who had confirmed complete response (CR) or partial response (PR) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
次要结局
- Phase 1a: Overall Response Rate (ORR)(Approximately 24 months)
- Phase 1a and 1b: Duration of Response (DOR)(Approximately 24 months)
- Phase 1a and 1b: Time to Response (TTR)(Approximately 24 months)
- Phase 1b: Progression-Free Survival (PFS)(Approximately 24 months)
- Phase 1b: Disease Control Rate (DCR)(Approximately 24 months)
- Phase 1a and 1b: Maximum observed plasma concentration (Cmax) of BG-60366(Twice in the first 3 months)
- Phase 1a and 1b: Time to reach maximum observed plasma concentration (Tmax) of BG-60366(Twice in the first 3 months)
- Phase 1a and 1b: Apparent terminal elimination half-life (t1/2) of BG-60366(Twice in the first 3 months)
- Phase 1a and 1b: Area under the concentration-time curve (AUC) for BG-60366(Twice in the first 3 months)
- Phase 1a and 1b: Minimum observed plasma concentration (Cmin) of BG-60366(Twice in the first 3 months)
- Phase 1a and 1b: Apparent total clearance (CL/F) of BG-60366(Twice in the first 3 months)
- Phase 1a and 1b: Apparent volume of distribution (Vz/F) of BG-60366(Twice in the first 3 months)
- Phase 1a and 1b: Accumulation Ratio (AR) of BG-60366(Once in the first three months)
- Phase 1a and 1b: Plasma concentrations of BG-60366(Approximately up to 6 months)