Histologically confirmed locally advanced (stage IIIB, IIIC ineligible for curative therapy) or metastatic KRAS G12C-mutant non-small cell lung cancer (NSCLC)
Conditions
Interventions
Test group:Glecirasib combined with Sacituzumab Tirumotecan
Sponsors
Peking Union Medical College Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed locally advanced (stage IIIB, IIIC not amenable to curative treatment) or metastatic non-small cell lung cancer (NSCLC); 2. Aged 18 to 75 years, male or female; 3. At least one measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Measurable lesions should not have received local therapies such as radiotherapy. Lesions within prior radiation fields may be selected as target lesions if disease progression is documented and RECIST 1.1 criteria are satisfied; 4. Documented KRAS G12C mutation detected via an approved testing assay; 5. Experienced disease progression following first-line standard therapy, with no prior administration of KRAS G12C inhibitors; 6. Expected survival of at least 12 weeks; 7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 within 7 days prior to study drug administration; 8. Radiographic disease progression occurred during or after the most recent treatment for locally advanced or metastatic disease; 9. Adequate organ and bone marrow function (no blood transfusion, recombinant human thrombopoietin or colony-stimulating factor administered within 2 weeks before the first dose), defined as follows: a) Hematology: absolute neutrophil count (ANC) >=1.5×10?/L, platelets (PLT) >=100×10?/L hemoglobin >=9 g/dL b) Liver function: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) =60 mL/min; 10. Female subjects of childbearing potential and male subjects with partners of childbearing potential must agree to use effective medical contraception from the date of informed consent signature through 6 months after the last study drug administration (see Appendix 1 for details); 11. Voluntarily enroll in this study, sign the informed consent form, demonstrate good treatment compliance, and agree to complete all follow-up procedures.
Exclusion criteria
Exclusion criteria: 1. Histological or cytological confirmation of mixed components including small cell lung cancer, neuroendocrine carcinoma, or carcinosarcoma within tumor specimens; 2. Subjects with known meningeal metastasis, brainstem metastasis, spinal cord metastasis and/or spinal cord compression, or active central nervous system (CNS) metastases without prior local therapy. Subjects with brain metastases previously treated with local therapy may be eligible if clinically stable for at least 4 weeks prior to study drug administration and no corticosteroids or anticonvulsants are required for at least 14 days before dosing; 3. Prior receipt of TROP2-targeted therapy, prior treatment with any topoisomerase I inhibitor, prior administration of any KRAS inhibitor; 4. Uncontrolled hypertension (systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg despite optimal medical management); 5. Persistent or active infectious disease; 6. Participation in another clinical trial of anti-tumor investigational products within 4 weeks prior to screening; 7. Presence of adverse events graded > Grade 1 per CTCAE (excluding alopecia) before the first study drug dose; 8. History of other untreated malignant tumors within the past 5 years (excluding cured basal cell carcinoma of the skin and cervical carcinoma in situ); 9. Subjects with active chronic inflammatory bowel disease, gastrointestinal obstruction, severe peptic ulcer, gastrointestinal perforation, intra-abdominal abscess, or acute gastrointestinal hemorrhage; 10. Active hepatitis B or hepatitis C infection; 11. Positive human immunodeficiency virus (HIV) test result or medical history of acquired immunodeficiency syndrome (AIDS) known active syphilis infection; 12. Known hypersensitivity to the study drugs or any of their excipients/components; 13. Medical history of non-infectious interstitial lung disease (ILD) or non-infectious pneumonitis requiring steroid treatment current active ILD or non-infectious pneumonitis or suspected ILD/non-infectious pneumonitis that cannot be radiographically ruled out at screening; 14. Clinically significant severe pulmonary impairment secondary to concurrent pulmonary comorbidities, including but not limited to any underlying lung disease (e.g., pulmonary embolism within 3 months prior to dosing, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc.), any autoimmune, connective tissue or inflammatory disease involving the lungs (i.e., rheumatoid arthritis, Sjögren’s syndrome, sarcoidosis, etc.), or prior pneumonectomy of the entire lung; 15. Poorly controlled diabetes mellitus (fasting blood glucose >=10 mmol/L on two consecutive measurements); 16. Symptomatic pleural effusion, pericardial effusion or ascites requiring repeated drainage (> once per week); 17. Documented severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or history of corneal disorders that impair delayed corneal wound healing; 18. Pregnant or lactating female subjects; 19. Any medical condition that, in the Investigator’s judgment, would interfere with the evaluation of the study drugs, compromise subject safety, or confound the interpretation of study results or any other condition rendering the subject unsuitable for enrollment as determined by the Investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| objective response rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| profession-free survial;disease control rate; | — |
Countries
China
Contacts
Public ContactWang Mengzhao
Peking Union Medical College Hospital
Outcome results
None listed