Non-small cell lung cancer
Conditions
Interventions
short course Sacituzumab Tirumotecan (Sac-TMT) plus PD-1 inhibitors :Patients will receive sac-TMT at a dose of 4mg/kg Q2W for 6 cycles and any of the investigator-selected PD-(L)1 inhibitors approved
Sponsors
Shanghai Geriatric Medical Center
Eligibility
Sex/Gender
All
Age
70 Years to No maximum
Inclusion criteria
Inclusion criteria: 1.Age >= 70 years, male or female.? 2.Geriatric 8 score >= 15.? 3.Histologically or cytologically confirmed locally advanced or metastatic (stage IIIB–IV) non-small cell lung cancer (NSCLC) who are ineligible for surgical treatment or radical concurrent/sequential chemoradiotherapy.? 4.Negative for EGFR sensitizing mutations (no exon 19 deletion or exon 21 L858R substitution) and negative for ALK fusion gene (for subjects with non-squamous NSCLC, non-smoking squamous NSCLC, or NSCLC with adenocarcinoma components, EGFR and ALK status must be histologically confirmed negative); no known driver gene alterations including ROS1, NTRK, and BRAF. For smoking subjects with squamous NSCLC, if prior EGFR and/or ALK status is unknown, testing is not required prior to enrollment and will be regarded as negative.? 5.No prior systemic therapy for advanced or recurrent disease. Subjects who received prior adjuvant/neoadjuvant chemotherapy or radical concurrent/sequential chemoradiotherapy are eligible if disease progression occurred >= 6 months after the last treatment.? 6.PD-L1 TPS >= 1%.? 7.ECOG performance status 0–1 within 7 days before study treatment initiation.? 8.Patients with brain metastases who received prior local therapy and have stable symptoms for >=4 weeks are eligible.? 9.At least one measurable lesion per RECIST 1.1 criteria.? 10.Life expectancy >=12 weeks.? 11.Adequate organ and bone marrow function (no blood transfusion, recombinant human thrombopoietin, or colony-stimulating factor administered within 2 weeks before first dose), defined as follows:? a) Hematology: absolute neutrophil count (NEUT#) >= 1.5×10^9/L; platelet count (PLT) >=100×10^9/L; hemoglobin >= 9 g/dL.? b) Hepatic function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 30 g/L; total bilirubin (TBIL) = 50 mL/min (calculated using the standard Cockcroft-Gault formula).? d) Coagulation: international normalized ratio (INR), activated partial thromboplastin time (APTT), and prothrombin time (PT) = 50% on echocardiogram (ECHO) or multigated acquisition (MUGA) scan.? 12.Subjects voluntarily participate in this study, provide written informed consent, demonstrate good compliance, and agree to comply with follow-up procedures.?
Exclusion criteria
Exclusion criteria: 1.Histologically or cytologically confirmed tumor with components of small cell lung cancer (SCLC), neuroendocrine carcinoma, or carcinosarcoma. 2.Prior treatment with TROP2-targeted therapies or topoisomerase I-targeted therapies (including ADC drugs). 3.Prior use of immune checkpoint inhibitors, including PD-(L)1 inhibitors. 4.Known hypersensitivity to the study drug or any of its components, or a history of severe hypersensitivity reactions to other biological agents. 5.Requirement for strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) within 2 weeks before the first dose and during the study. (The use of strong 6.CYP3A4 inhibitors or inducers is prohibited in this study. Representative drugs are listed in Appendix 5.) All subjects must avoid concomitant use of any medications, herbal supplements, and/or consumption of foods known to induce CYP3A4. 7.Subjects with known leptomeningeal metastases, brainstem metastases, spinal cord metastases and/or compression, or active/untreated central nervous system (CNS) metastases. Subjects with previously treated brain metastases may participate if clinically stable for at least 4 weeks prior to dosing and off corticosteroids or anticonvulsants for at least 14 days. 8.Uncontrolled systemic diseases as judged by the investigator: a) Poorly controlled diabetes mellitus (fasting blood glucose >= 10 mmol/L on two consecutive occasions). b) Poorly controlled hypertension (systolic BP > 160 mmHg and/or diastolic BP > 100 mmHg). c) Clinically significant pleural effusion, pericardial effusion, or ascites requiring frequent drainage (> once/week). 9.Severe infection (including complications requiring hospitalization, sepsis, or severe pneumonia) within 4 weeks before the first dose; active infection requiring systemic antimicrobial therapy within 2 weeks before the first dose. 10.History of (non-infectious) interstitial lung disease (ILD) or non-infectious pneumonia requiring steroids; current ILD or non-infectious pneumonia; or suspected ILD or non-infectious pneumonia on screening imaging that cannot be ruled out. 11.Documented severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or a history of corneal disease that impairs delayed corneal healing. 12.Clinically significant pulmonary impairment due to concurrent lung diseases. 13.Tumor invading or compressing vital organs and vessels (e.g., heart, esophagus, superior vena cava) with associated symptoms (e.g., superior vena cava syndrome), or at risk of esophagotracheal fistula or esophagopleural fistula. 14.Concurrent diseases and medical history: a) Other malignancies (past or concurrent) within 5 years, except cured basal cell carcinoma of the skin, carcinoma in situ of the cervix, and superficial bladder cancer. b) Adverse events from prior therapy (except alopecia) that have not resolved to CTCAE Grade <= 1. c) Major surgical procedure or significant traumatic injury within 28 days before the first dose. d) Arterial/venous thrombotic event within 6 months. 15.Active autoimmune disease requiring systemic therapy in the past 2 years (hormone replacement therapy is not considered systemic therapy). History of autoimmune diseases (except autoimmune-related hypothyroidism and controlled type 1 diabetes), idiopathic pulmonary fibrosis (IPF), organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or active pneumonia; known HIV-positive; known active hepatitis B or C; or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate (ORR); | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression-Free Survival (PFS);Disease Control Rate(DCR); Overall Survival(OS);Safety and tolerability: including incidence and severity of adverse events, drug-relatedness, dose modification/discontinuation, vital signs and laboratory parameter changes, etc.; | — |
Countries
China
Contacts
Public ContactHu Jie
Shanghai Geriatric Medical Center
Outcome results
None listed