Clinical Trial of Lurbinectedin as Single-agent or in Combination With Irinotecan Versus Topotecan or Irinotecan in Patients With Relapsed Small-cell Lung Cancer (LAGOON)

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 pleural or cardiac effusion rapidly increasing and/or necessitating prompt local treatment within seven days.
• •14. Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study (e.g.; COVID-19 disease).
• •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 inactivated 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 a highly effective method of contraception