EGFR Activating Mutation, EGFR Mutation-Related Tumors, Lung Cancer, Non-Small Cell Lung Cancer, NSCLC, NSCLC (Non-small Cell Lung Carcinoma)
Conditions
Keywords
lung cancer, non-small cell lung cancer, NSCLC, EGFR activating mutation, EGFR resistant mutation, advanced or metastatic non-small cell lung cancer
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
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.
Interventions
DRUGBG-60366
Administered orally
Sponsors
BeOne Medicines
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 | — |
Countries
Australia, China, Italy, New Zealand, South Korea, Spain, United States
Contacts
STUDY_DIRECTORStudy Director
BeOne Medicines
Outcome results
None listed