Study of Lurbinectedin in Combination With Doxorubicin Versus Doxorubicin Alone as First-line Treatment in Participants With Metastatic Leiomyosarcoma (SaLuDo)

Exclusion Criteria

• •1. Prior treatment with anthracyclines, lurbinectedin or trabectedin.
• •2. Known low grade leiomyosarcoma (i.e., grade I).
• •3. Known hypersensitivity to any of the components of the IV formulation of lurbinectedin or doxorubicin.
• •4. Concomitant diseases/conditions:
• •1. History of cardiac disease: myocardial infarction or angina within the year prior to enrollment; severe vascular disease; or symptomatic arrhythmia despite ongoing treatment.
• •2. Participants with any immunodeficiency, including those known to be infected by human immunodeficiency virus (HIV).
• •3. Known chronic active hepatitis or cirrhosis. For Hepatitis B, this includes positive tests for both Hepatitis B surface antigen 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.
• •4. Active uncontrolled infection.
• •5. Any other major illness that (including severe cardiovascular disease) or risk factors that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.
• •5. Use of strong inducers of CYP3A4 activity within two weeks prior to the first infusion of lurbinectedin.
• •6. Prior irradiation of a RECIST v.1.1 target lesion if only one target lesion is available, unless progression of the lesion has been confirmed.
• •7. Known myopathy (history of resolved steroid-induced myopathy is allowed).
• •8. History of malignancies other than LMS within three years prior to enrollment, except for malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate \>90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, non-muscle-invasive urothelial carcinomas, ductal carcinoma in situ, or stage I uterine cancer. Prior malignancies should have received curative treatment and should remain in remission. The Investigator should ensure, based on histology or clinical information, that the current metastatic sites are leiomyosarcoma and not recurrence of the original malignancy.
• •9. Limitation of the participant's ability to comply with the treatment or to follow-up the protocol.
• •10. Women who are pregnant or breast feeding and fertile participants (men and women) who are not using a highly effective method of contraception.
• •11. Participants in whom rapid tumor shrinkage is needed (e.g., when a tumor is close to a critical structure).