Approximately 705 Adult SCLC patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2 who have failed one prior platinum-containing line with CTFI ≥ 30 days and controlled asymptomatic Central Nervous System metastases will be enrolled and assigned to each treatment arm.

Central randomization will be implemented; patients will be assigned to each treatment arm at a 1:1:1 ratio.

An Independent Data Monitoring Committee (IDMC) will oversee the conduct of the study. The IDMC should have access to unblinded efficacy and safety data throughout the trial to enable timely and informed judgments about risks and benefits.

Inclusion Criteria:

1. Voluntary written informed consent of the patient obtained before any study-specific procedure
2. Age≥18 years
3. Histologically or cytologically confirmed diagnosis of SCLC.
4. One prior line of platinum-containing chemotherapy with/without anti-PD-1 or anti-PD-L1 (Note: at least 70% of patients included in the study have to be pretreated with anti-PD-1 or anti-PD-L1)
5. Chemotherapy-free interval (CTFI, time from the last dose of first-line platinum-containing chemotherapy to the occurrence of progressive disease) ≥ 30 days (independent of the immunotherapy maintenance, if applicable)
6. Patients with history of Central Nervous System (CNS) metastases can participate provided they are pretreated and radiologically stable (i.e., without evidence of progression) for at least 4 weeks by repeated imaging (note: repeated imaging should be performed during study screening), asymptomatic, and without requirement of steroid treatment for at least 7 days before the first dose of study treatment
7. Eastern Cooperative Oncology Group (ECOG) PS ≤ 2
8. Adequate hematological, renal, metabolic and hepatic function:
   1. Hemoglobin ≥ 9.0 g/dL [patients may have received prior red blood cell (RBC) transfusion, if clinically indicated]; absolute neutrophil count (ANC) ≥ 2.0 x 10^9/L, and platelet count ≥ 100 x 10^9/L.
   2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x upper limit of normal (ULN).
   3. Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN.
   4. Albumin ≥ 3.0 g/dL.
   5. Calculated creatinine clearance (CrCL) ≥ 30 mL/min (using Cockcroft and Gault's formula).
9. At least three weeks since last prior antineoplastic treatment and recovery to grade ≤ 1 from any adverse event (AE) related to previous anticancer treatment (excluding sensory neuropathy, anemia, asthenia and alopecia, all grade ≤ 2) according to the National Cancer InstituteCommon Terminology Criteria for Adverse Events (NCICTCAE) v.5.
10. Prior radiotherapy (RT): At least two weeks since completion of prophylactic cranial irradiation (PCI), and to any other site not previously specified.
11. Evidence of non-childbearing status for women of childbearing potential (WOCBP). WOCBP must agree to use a highly effective contraceptive measure up to six months after treatment discontinuation. Fertile male patients with WOCBP partners should use condoms during treatment and for four months following the last investigational medicinal product (IMP) dose.

Exclusion Criteria:

1. Platinum-naïve patients or patients pretreated with more than one prior chemotherapy regimen (including patients re-challenged with same initial regimen).
2. Prior treatment with lurbinectedin, trabectedin, PM14, or topoisomerase I inhibitors (irinotecan, topotecan, etc.).
3. Active or untreated CNS metastases and/or carcinomatous meningitis.
4. Patients with limited-stage disease who are candidates for local or regional therapy, including PCI, thoracic RT or both, must have been offered that option and completed treatment or refused it prior to randomization.
5. Concomitant diseases/conditions:
   1. History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within last year.
   2. Symptomatic arrhythmia or any uncontrolled arrhythmia requiring ongoing treatment.
   3. Ongoing chronic alcohol consumption or cirrhosis with Child-Pugh score B or C.
   4. Known Gilbert's disease.
   5. Active uncontrolled infection. Serious non-healing wound, ulcer or bone fracture. Presence of external drainages.
   6. Ongoing, treatment-requiring, non-neoplastic chronic liver disease of any origin. For Hepatitis B, this includes positive tests for both Hepatitis B surface antigen (HBsAg) and quantitative Hepatitis B polymerase chain reaction (PCR). For Hepatitis C, this includes positive tests for both Hepatitis C antibody and quantitative Hepatitis C PCR. Subjects taking hepatitis related antiviral therapy within six months prior to the first dose of study drugs will also be excluded.
   7. Intermittent or continuous oxygen requirement within two weeks prior to randomization. Patients with confirmed or suspected diagnosis of diffuse interstitial lung disease or pulmonary fibrosis.
   8. Patients with a second invasive malignancy treated with chemotherapy and/or RT. Patients with a previous malignancy that was completely resected with curative intention three or more years prior to randomization, except treated in situ carcinoma of the cervix, basal or squamous cell skin carcinoma, and in situ transitional cell bladder carcinoma and who has been continuously in remission since then will be permitted.
   9. Limitation of the patient's ability to comply with the treatment or to follow the protocol.
   10. Documented or suspected invasive fungal infections requiring systemic treatment within 12 weeks of randomization.
   11. Known human immunodeficiency virus (HIV) infection.
   12. Any past or present chronic inflammatory colon and/or liver disease, past intestinal obstruction, pseudo or subocclusion or paralysis.
   13. Evident symptomatic pulmonary fibrosis or interstitial pneumonitis, pleural or cardiac effusion rapidly increasing and/or necessitating prompt local treatment within seven days.
   14. Active COVID-19 disease (this includes positive test for SARS-CoV-2 in nasopharyngeal/oropharyngeal swabs or nasal swabs by PCR).
   15. Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.
6. RT in more than 35% of the bone marrow.
7. History of previous bone marrow and/or stem cell transplantation and allogenic transplant.
8. Patient has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
9. Impending need for RT (e.g., painful bone metastasis and/or risk of spinal cord compression).
10. History of allergy or hypersensitivity to any of the study drugs or any of their excipients.
11. Women who are pregnant or breast feeding and fertile patients (men and women) who are not able to use an effective method of contraception