Lurbinectedin Plus Paclitaxel Versus Paclitaxel in Patients With Previously Treated Small Cell Lung Cancer

Inclusion criteria

• Age ≥ 19 years.
• Histologically or cytologically confirmed extensive-stage small cell lung cancer (ES-SCLC).
• Patients who have experienced disease progression following at least one prior platinum-based systemic therapy for extensive-stage small cell lung cancer, including all of the following conditions:

• Patients who failed treatment within 6 months after curative-intent chemotherapy are considered as having failed first-line therapy.
• For platinum-sensitive patients, participation in the third-line cohort is allowed after re-treatment with a platinum-based regimen as second-line therapy (limited-stage).
• For platinum-resistant patients, participation in the second-line cohort is allowed (limited-stage).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• At least one measurable target lesion according to RECIST v1.1 criteria.
• Predicted life expectancy of at least 12 weeks (3 months).
• Adequate hematologic, renal, metabolic, and hepatic function within 14 days prior to enrollment, defined as:

Absolute neutrophil count (ANC) ≥ 1,500/μL Platelet count ≥ 100,000/μL Hemoglobin (Hb) ≥ 9.0 g/dL Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or calculated creatinine clearance (cCr) ≥ 60 mL/min Total bilirubin ≤ 1.0 × ULN AST and ALT ≤ 3.0 × ULN (regardless of liver metastasis) PT and aPTT ≤ 1.5 × ULN

• Willingness to provide unstained slides (minimum 5, ideally 15) from archived or freshly biopsied tissue for exploratory analyses.
• Female participants of childbearing potential must have a negative pregnancy test (urine) at screening. If the urine test is positive or inconclusive, a negative serum pregnancy test is required.

Female participants of childbearing potential must agree to use effective contraception during the study.

• Male participants of reproductive potential must agree to use effective contraception during the study (see appendix for acceptable methods).
• Voluntary written informed consent to participate in this clinical trial.

Exclusion criteria

• Patients who have not received prior systemic therapy for small cell lung cancer (SCLC).
• Patients previously treated with Lurbinectedin or Paclitaxel.
• Patients with limited-stage small cell lung cancer (LS-SCLC).
• Patients with symptomatic or clinically significant brain metastases (patients with asymptomatic or stable brain metastases may be eligible; any treatment for brain metastases must have been completed at least 1 week prior to the first dose of study drug).
• Concomitant use of medications that may prolong the QTc interval, potent immunosuppressive agents, or drugs that may cause interstitial lung disease (ILD) is prohibited during the treatment period. If co-administration is unavoidable, prior discussion with the coordinating center is required.
• Patients with active primary immunodeficiency (e.g., HIV infection), active hepatitis B, or active hepatitis C:

• HBsAg-positive patients may be eligible if HBV DNA is negative or appropriate antiviral therapy is being administered.
• HCV antibody-positive patients may be eligible if HCV RNA is negative or the patient has been cured after treatment.
• Patients with active interstitial lung disease (ILD) or a history of non-infectious pneumonitis requiring steroid therapy, including immune-therapy- or chemotherapy-related ILD or Grade ≥3 pulmonary complications. (Patients with previously resolved infectious pneumonia without current clinical significance may be eligible.)
• Pregnant or breastfeeding women.
• Patients with clinically significant cardiovascular disease within the past 12 months (e.g., congestive heart failure, symptomatic coronary artery disease, arrhythmias, myocardial infarction).
• Patients whose toxicities from prior anticancer therapy have not recovered to baseline or ≤ Grade 2.
• Patients who received any prior anticancer therapy within 14 days or localized radiotherapy within 7 days before the first dose of the study drug.
• Patients with a known hypersensitivity to the study drugs.
• Any condition that, in the opinion of the investigator, makes the patient unsuitable for participation in the study.