EGFR Mutant non-small cell lung cancer
Conditions
Interventions
Part 1(1a Dose escalation and safety expension):BG-60366
Part 2 (1b dose expension):BG-60366
Sponsors
Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Patients must sign the informed consent form and be able to provide written informed consent (i.e., able to comply with the requirements and restrictions listed in the ICF and this protocol); 2. Patients must be >= 18 years old (or at the legal age of consent in the region of the study) at the time of signing the informed consent form; 3. Histologically or cytologically confirmed NSCLC with an EGFR activating mutation (e.g., exon 19 deletion, L858R, G719X, L861Q, or S768I mutation) prior to receiving standard EGFR-TKI treatment; 4. Part 1, Phase 1a dose escalation: advanced or metastatic disease with disease progression after prior third-generation EGFR-TKI treatment (or disease progression after prior first-/second-generation EGFR-TKI treatment without T790M mutation), and based on investigator judgment, progression after currently available standard therapy (e.g., platinum-based chemotherapy) following EGFR-TKI treatment, or no available standard therapy; 5. Part 1, Phase 1a safety expansion: (1) Documented evidence of EGFR resistance mutations (Appendix 9); (2) Advanced or metastatic disease with disease progression after prior third-generation EGFR-TKI treatment, and progression after currently available standard therapy (e.g., platinum-based chemotherapy) following EGFR-TKI treatment, or no available standard therapy. Note: In countries where third-generation EGFR-TKIs are unavailable, patients with acquired T790M resistance mutation after first-/second-generation EGFR-TKI treatment, and progression after currently available standard therapy (e.g., platinum-based chemotherapy) or no available standard therapy, are also eligible for enrollment; 6. Part 2, Phase 1b dose expansion cohort A: (1) Documented evidence of EGFR-dependent resistance mutations (see Appendix 9 for EGFR-dependent resistance mutations); (2) Advanced or metastatic disease with disease progression after previous third-generation EGFR-TKI treatment, and subsequent treatment with platinum-based chemotherapy following progression; 7. Part 2, Phase 1b dose expansion cohort B: (1) No documented evidence of EGFR-dependent resistance mutations through EGFR mutation testing. Patients eligible for cohort A refer to Appendix 9 for EGFR-dependent resistance mutations. Note: Patients with EGFR-independent resistance mutations or undetected resistance mechanisms are eligible for cohort B; (2) Advanced or metastatic tumors with disease progression after prior third-generation EGFR-TKI treatment, and subsequent progression following a platinum-based chemotherapy regimen or no available chemotherapy; 8. Part 2, Phase 1b Dose Expansion Cohort C: (1) There is documented evidence of EGFR C797X resistance mutation (either alone or in combination with other EGFR resistance mutations); (2) Advanced or metastatic disease has progressed following prior treatment with a third-generation EGFR-TKI; 9. Part 2, Phase 1b Dose Expansion Cohort D: (1) There is documented evidence of non-C797X EGFR resistance mutations (see Appendix 9); (2) Advanced or metastatic NSCLC has progressed following prior treatment with a third-generation EGFR-TKI. Note: In countries where third-generation EGFR-TKIs are not available, patients who have progressed on prior first- or second-generation EGFR-TKI therapy are also eligible if a T790M resistance mutation is present; 10. For Phase 1a dose escalation, patients must have >=1 evaluable lesion as defined by RECIST 1.1; for the safety expansion
Exclusion criteria
Exclusion criteria: 1. Any histological or cytological evidence of prior small cell or combined small cell/non-small cell disease found in archived tumor tissue or tumor biopsy before enrollment; 2. For Cohorts C and D in the dose expansion phase, patients with advanced or metastatic NSCLC who received any systemic anticancer therapy (such as chemotherapy) after disease progression on third-generation EGFR-TKI therapy are not allowed to enroll in Cohorts C and D; 3. Symptomatic spinal cord compression (patients can enroll if steroid treatment is not required for at least 2 weeks before the first dose of the study drug); 4. Symptomatic and/or urgently treatable brain metastases (e.g., beginning steroids or stereotactic radiosurgery/whole-brain radiotherapy within 2 weeks before the first dose of the study drug); 5. Prior treatment with fourth-generation EGFR-TKIs, other EGFR mutation-targeting CDAC/PROTACs, or drugs targeting specific EGFR resistance mutations (such as C797X) (excluding first- to third-generation EGFR-TKIs); 6. Any history of interstitial lung disease within = Grade 2 non-infectious pulmonary inflammation, or current interstitial lung disease/non-infectious pulmonary inflammation, or patients in whom suspected active interstitial lung disease/non-infectious pneumonia cannot be ruled out by imaging at screening; 7. Poorly controlled pleural effusion, pericardial effusion, or ascites requiring frequent drainage (clinically significant recurrence = 470 ms on three consecutive ECGs during the screening period, and a history or condition with risk factors for torsades de pointes (such as NYHA class III–IV heart failure [Appendix 7], >= Grade 2 poorly controlled hypokalemia, or a family history of long QT syndrome).; 9. Has any of the following cardiovascular risk factors: (1) Experienced a ventricular arrhythmia event of severity >= Grade 2 within = Grade 3) unmanageable with standard antihypertensive treatment within =14 days before the first dose of the study drug are eligible for re-screening; 11. Experienced an active infection requiring systemic (intravenous) antibacterial, antifungal, or antiviral therapy (including tuberculosis infection) within <=14 days before the first dose of the study drug; Note: Patients receiving prophylactic antibiotics (e.g., for prevention of urinary tract infection, chronic obstructive pulmonary disease, or post-tooth extraction prevention) are eligible for the study; 12. History of severe allergic or hypersensitivity reactions to the active ingredients or excipients of the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse events, serious adverse events;Maximum Tolerated Dose (MTD) or Maximum Administration Dose (MAD) and Extended Recommended Dose (RDFE); | — |
Secondary
| Measure | Time frame |
|---|---|
| Duration of Response;Objective Response Rate ;Time to Response;Progression-Free Survival;Disease Control Rate ; | — |
Countries
China
Contacts
Public ContactZhou Qing
Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)
Outcome results
None listed