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

Inclusion Criteria:

1. Voluntary signed and dated written informed consent of the participants obtainedbefore any study-specific procedure.

2. Age ≥ 18 years.

3. Histologically confirmed diagnosis of metastatic LMS, in participants not candidatesfor curative resection.

4. Radiologically measurable disease according to the Response Evaluation Criteria inSolid Tumors (RECIST) v.1.1.

5. No previous systemic therapy for metastatic disease (i.e., first-line setting) andno previous anthracyclines. Note: prior chemotherapy (without anthracycline) in thecontext of adjuvant or neoadjuvant therapy is allowed. Prior line/s of hormonetherapy in the adjuvant/metastatic setting are also allowed.

6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1.

7. Adequate hematological, renal, metabolic and hepatic function:

8. Hemoglobin ≥ 9.0 g/dL (participants may have received prior red blood cell [RedBlood Cell] transfusion); absolute neutrophil count (ANC) ≥ 2.0 x 10^9/L, andplatelet count ≥ 100 x 10^9/L.

9. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 xupper limit of normal (ULN).

10. Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN if total bilirubin is >ULN.

11. Albumin ≥ 3.0 g/dL.

12. Calculated creatinine clearance (CrCL) ≥ 30 mL/min (using Cockcroft and Gault'sformula).

13. Left ventricular ejection fraction (LVEF) > 50% assessed by multiple-gatedacquisition scan (MUGA) or echocardiography (ECHO) or cardiac magneticresonance imaging (MRI).

14. Wash-out periods:

15. At least three weeks since last prior systemic treatment.

16. At least three weeks since last prior major surgery and one week since lastprior minor surgery (port placement is excluded from this wash-out period).

17. At least two weeks since last prior radiotherapy.

18. Evidence of non-childbearing status for women of childbearing potential (WOCBP).WOCBP must agree to use a highly effective contraceptive measure up to seven monthsafter treatment discontinuation. Fertile male participants with WOCBP partnersshould use condoms during treatment and for four months following the lastinvestigational medicinal product (IMP) dose.

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 oflurbinectedin or doxorubicin.

4. Concomitant diseases/conditions:

5. History of cardiac disease: myocardial infarction or angina within the yearprior to enrollment; severe vascular disease; or symptomatic arrhythmia despiteongoing treatment.

6. Participants with any immunodeficiency, including those known to be infected byhuman immunodeficiency virus (HIV).

7. Known chronic active hepatitis or cirrhosis. For Hepatitis B, this includespositive tests for both Hepatitis B surface antigen and quantitative HepatitisB polymerase chain reaction (PCR). For Hepatitis C, this includes positivetests for both Hepatitis C antibody and quantitative Hepatitis C PCR.

8. Active uncontrolled infection.

9. Any other major illness that (including severe cardiovascular disease) or riskfactors that, in the Investigator's judgment, will substantially increase therisk associated with the patient's participation in this study.

10. Use of strong inducers of CYP3A4 activity within two weeks prior to the firstinfusion of lurbinectedin.

11. Prior irradiation of a RECIST v.1.1 target lesion if only one target lesion isavailable, unless progression of the lesion has been confirmed.

12. Known myopathy (history of resolved steroid-induced myopathy is allowed).

13. 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-yearOS rate >90%), such as adequately treated carcinoma in situ of the cervix,non-melanoma skin carcinoma, localized prostate cancer, non-muscle-invasiveurothelial carcinomas, ductal carcinoma in situ, or stage I uterine cancer. Priormalignancies should have received curative treatment and should remain in remission.The Investigator should ensure, based on histology or clinical information, that thecurrent metastatic sites are leiomyosarcoma and not recurrence of the originalmalignancy.

14. Limitation of the participant's ability to comply with the treatment or to follow-upthe protocol.

15. Women who are pregnant or breast feeding and fertile participants (men and women)who are not using a highly effective method of contraception.

16. Participants in whom rapid tumor shrinkage is needed (e.g., when a tumor is close toa critical structure).