SMARCA4-deleted advanced non-small cell lung cancer without sensitive gene mutations that failed front-line treatment
Conditions
Interventions
Treatment group:Sacituzumab Tirumotecan for Injection
Sponsors
Shanghai Pulmonary Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1.Age >=18 years old at the time of signing the informed consent form, regardless of gender; 2.Locally advanced (stage IIIB/IIIC) or metastatic (stage IV) NSCLC that is not suitable for radical surgery and/or radical radiotherapy (whether or not concurrent chemotherapy is received)[according to the International League Against Cancer and the American Joint Committee on Cancer (AJCC) Lung Cancer TNM Staging, 8th Edition]; 3.Immunohistochemistry (IHC) confirmed the deletion of BRG1 protein (encoded by the SMARCA4 gene); 4.No other sensitive mutations (including EGFR, ALK, ROS1, RET, c-Met, HER2, BRAF genes); 5.Previously received standard treatment with first-line immune checkpoint inhibitors alone or platinum-containing dual drug chemotherapy combined with immune checkpoint mode, and demonstrated imaging confirmed disease progression during or after treatment; 6.The subject's brain metastasis status at the time of enrollment must meet one of the following conditions: a) No brain metastases; b) Stable brain metastases, defined as the absence of central nervous system symptoms; or clinically stable for at least 4 weeks prior to enrollment, with all central nervous system symptoms returning to baseline status; no evidence of new or expanding brain metastases; and no treatment with glucocorticoids or anticonvulsants for at least 2 weeks prior to enrollment; 7.At least one measurable target lesion without radiotherapy was assessed by the investigator according to RECIST v1.1; 8.Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; 9.Expected survival >= 12 weeks; 10.Adequate organ and bone marrow function (no blood transfusion, recombinant human thrombopoietin, or colony stimulating factor treatment within 2 weeks prior to the first dose), defined as follows: a) Blood routine: Neutrophils count (NEUT) = 1.5×10^9/L; platelets (PLT) >= 100×10^9/L; hemoglobin >= 100 g/L; b) liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 30g/L; for subjects with liver metastases at baseline, ALT and AST= 50 ml/min (calculated using the standard Cockcroft-Gault formula); d) Coagulation function: International normalized ratio (INR), activated partial thromboplastin time (APTT) and prothrombin time (PT) <= 1.5×ULN; 11.For female subjects of childbearing potential and male subjects with partners of childbearing potential, they must agree to use effective medical contraceptive measures from the time of signing the informed consent form to 6 months after the last dose; 12.Subjects voluntarily joined the study, signed informed consent forms, and were able to comply with the visits and related procedures specified in the protocol.
Exclusion criteria
Exclusion criteria: 1.Participated in clinical trials of other drugs within 4 weeks before enrollment; 2.Previous treatment targeting TROP2 or any drug therapy containing targeted topoisomerase I, including antibody-coupled drug (ADC) therapy (including in the context of adjuvant, neoadjuvant therapy); 3.Having other malignant tumors within 3 years before the first dose (except for tumors that have been cured through local treatment, such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, etc.); 4.When patients are receiving rukangsartuzumab in combination with immune checkpoint inhibitors, patients who have experienced any of the following while receiving first-line immune checkpoint inhibitors in previous first-line therapy will be excluded: a. Progress within 3 months after the start of treatment; b. Previous Grade 3 and above adverse reactions, Grade 2 immune-related cardiotoxicity, or any grade neurological or ocular adverse reactions caused by PD-1 inhibitor treatment; c. Prior to screening in this study, all adverse events with previous PD-1 inhibitor treatment had not been completely resolved or had not resolved to Grade 1; d. Previous adverse events requiring treatment with other immunosuppressants other than glucocorticoids; 5.A known history of allergy to rukangsartuzumab and its components; 6.Positive human immunodeficiency virus (HIV) test or a history of acquired immunodeficiency syndrome (AIDS); known active syphilis infection; 7.Have a history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation; 8.Received a live vaccine within 30 days prior to the first study dose; 9.History of (non-infectious) interstitial lung disease (ILD) or non-infectious pneumonia requiring steroid treatment, current ILD or non-infectious pneumonia, or suspected ILD or non-infectious pneumonia at screening that cannot be ruled out by imaging; Clinical severe lung damage caused by concurrent lung disease, including but not limited to any underlying lung disease (such as pulmonary embolism, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc. within 3 months prior to dosing) or any autoimmune, connective tissue or inflammatory disease that may affect the lungs (ie, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.), or previous pneumonectomy; 10.Those who require the use of strong inhibitors or inducers of the cytochrome P450 3A4 enzyme (CYP3A4) within 2 weeks before the first dose and during the study (the use of strong inhibitors or inducers of CYP3A4 is not allowed in this study); all subjects must try to avoid the concomitant use of any drugs, herbal supplements, and/or ingestion of such foods that are known to induce CYP3A4; 11.Having an active autoimmune disease that requires systemic treatment within the past 2 years (hormone replacement therapy is not considered systemic treatment, such as type 1 diabetes, hypothyroidism that requires only thyroxine replacement therapy, adrenal or pituitary dysfunction that requires only physiological doses of glucocorticoid replacement therapy); 12.Active infection requiring systemic treatment within 2 weeks before the first dose; 13.According to the investigator's judgment, there are serious concomitant diseases that endanger the patient's safety or affect the patient's completion of the study, including but not limited to hypertension that cannot be cont
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Disease control rate;Duration of response;Progression-free survival;Overall survival;Safety; | — |
Countries
China
Contacts
Public ContactJie Zhang
Shanghai Pulmonary Hospital
Outcome results
None listed