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

Lurbinectedin in Combination With Paclitaxel Versus Paclitaxel for Patients With Previously Treated Small Cell Lung Cancer: Randomized, Phase II, Open-label, Multi-center, Prospective Trial(LUPINE)

This clinical trial is designed to compare and evaluate the efficacy and safety of the combination therapy of Lurbinectedin plus Paclitaxel (Combination Arm) versus Paclitaxel monotherapy (Monotherapy Arm) in patients with extensive-stage small-cell lung cancer whose disease has progressed after first-line chemotherapy.

Inclusion Criteria:

1. Age ≥ 19 years.

2. Histologically or cytologically confirmed extensive-stage small cell lung cancer (ES-SCLC).

3. 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).

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

5. At least one measurable target lesion according to RECIST v1.1 criteria.

6. Predicted life expectancy of at least 12 weeks (3 months).

7. 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

8. Willingness to provide unstained slides (minimum 5, ideally 15) from archived or freshly biopsied tissue for exploratory analyses.

9. 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.

10. Male participants of reproductive potential must agree to use effective contraception during the study (see appendix for acceptable methods).

11. Voluntary written informed consent to participate in this clinical trial.

Exclusion Criteria:

1. Patients who have not received prior systemic therapy for small cell lung cancer (SCLC).

2. Patients previously treated with Lurbinectedin or Paclitaxel.

3. Patients with limited-stage small cell lung cancer (LS-SCLC).

4. 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).

5. 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.

6. 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.

7. 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.)

8. Pregnant or breastfeeding women.

9. Patients with clinically significant cardiovascular disease within the past 12 months (e.g., congestive heart failure, symptomatic coronary artery disease, arrhythmias, myocardial infarction).

10. Patients whose toxicities from prior anticancer therapy have not recovered to baseline or ≤ Grade 2.

11. Patients who received any prior anticancer therapy within 14 days or localized radiotherapy within 7 days before the first dose of the study drug.

12. Patients with a known hypersensitivity to the study drugs.

13. Any condition that, in the opinion of the investigator, makes the patient unsuitable for participation in the study.