A Study Investigating BG-60366 in Adults With Epidermal Growth Factor Receptor (EGFR)-Mutant Non-Small Cell Lung Cancer
- Conditions
- Non-Small Cell Lung CancerLung CancerNSCLCNSCLC (Non-small Cell Lung Carcinoma)EGFR Activating MutationEGFR Mutation-Related Tumors
- Interventions
- Drug: BG-60366
- Registration Number
- NCT06685718
- Lead Sponsor
- BeiGene
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 93
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Histologically or cytologically confirmed diagnosis of NSCLC, carrying an EGFR activating mutation prior to receiving standard EGFR-tyrosine kinase inhibitor (EGFR-TKI)
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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
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Phase 1a safety expansion
- Documentation of EGFR resistance mutations (ie, C797s)
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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
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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
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Adequate organ function
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Stable Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1a: Dose Escalation and Safety Expansion BG-60366 Sequential cohorts of increasing dose levels of BG-60366 will be evaluated as monotherapy. Phase 1b: Dose Expansion BG-60366 Recommended Dose(s) for Expansion (RDFE\[s\]) of BG-60366 as monotherapy determined from Phase 1a will be evaluated.
- Primary Outcome Measures
Name Time Method Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) 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) 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 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 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) 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.
- Secondary Outcome Measures
Name Time Method 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 Phase 1a and 1b: Apparent terminal elimination half-life (t1/2) 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: Overall Response Rate (ORR) Approximately 24 months ORR is defined as the percentage of participants who had confirmed CR or PR assessed by the investigator using RECIST v1.1.
Phase 1a and 1b: Duration of Response (DOR) Approximately 24 months DOR is defined as the time from the first determination of objective response that is confirmed by the subsequent assessment until the first documentation of disease progression or death, whichever comes first.
Phase 1a and 1b: Time to Response (TTR) Approximately 24 months TTR is defined as the time from the date of the first dose of study drugs to the date of teh first determination of objective response that is confirmed by the subsequent assessment.
Phase 1b: Progression-Free Survival (PFS) Approximately 24 months PFS is defined as the time from the date of the first dose of study drug to the date of the first documentation of disease progression assessed by the investigator using RECIST v1.1 or death, whichever occurs first.
Phase 1b: Disease Control Rate (DCR) Approximately 24 months DCR is defined as the percentage of participants with the best overall response of confirmed CR, PR, or stable disease assessed.
Phase 1a and 1b: Maximum observed plasma concentration (Cmax) of BG-60366 Twice in the first 3 months
Trial Locations
- Locations (19)
University of Colorado
🇺🇸Denver, Colorado, United States
University of Miami
🇺🇸Miami, Florida, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Washington University School of Medicine Siteman Cancer Center
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center Mskcc
🇺🇸New York, New York, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
The University of Texas Md Anderson Cancer Center
🇺🇸Houston, Texas, United States
Blacktown Cancer and Haematology Centre
🇦🇺Blacktown, New South Wales, Australia
Liverpool Hospital
🇦🇺Liverpool, New South Wales, Australia
Princess Alexandra Hospital
🇦🇺Brisbane, Queensland, Australia
Cancer Research South Australia
🇦🇺Adelaide, South Australia, Australia
Austin Health
🇦🇺Heidelberg, Victoria, Australia
Peter Maccallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Guangdong Provincial Peoples Hospital Huifu Branch
🇨🇳Guangzhou, Guangdong, China
The Second Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
Tianjin Medical University Cancer Institute and Hospital
🇨🇳Tianjin, Tianjin, China
Sarawak General Hospital
🇲🇾Kuching, Malaysia
Harbour Cancer and Wellness
🇳🇿Auckland, New Zealand
Vajira Hospital
🇹🇭Bangkok, Thailand