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

Inclusion Criteria:

1. Participant signed and dated written informed consent of the patient obtained beforeany study-specific procedure.

2. Age ≥ 18 years.

3. Histologically confirmed diagnosis of metastatic LMS.

4. Radiologically measurable disease according to the 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.

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

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

8. Hemoglobin ≥ 9.0 g/dL (patients may have received prior red blood cell [RBC]transfusion); absolute neutrophil count (ANC) ≥ 2.0 x 10^9/L, and plateletcount ≥ 100 x 109/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).

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.

17. At least two weeks since last prior radiotherapy.

18. Evidence of non-childbearing status for women of childbearing potential (WOCBP).

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 i.v. formulation oflurbinectedin or doxorubicin.

4. Concomitant diseases/conditions:

5. History of cardiac disease: myocardial infarction or unstable angina within theyear prior to enrollment; or symptomatic or uncontrolled arrhythmia despiteongoing treatment.

6. Patients 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, in the Investigator's judgment, willsubstantially increase the risk associated with the patient's participation inthis study.

10. Use of strong or moderate inhibitors or strong inducers of CYP3A4 activity withintwo weeks prior to the first infusion of lurbinectedin.

11. Prior irradiation if only one target lesion (i.e., measurable) is available, unlessprogression of the lesion has been confirmed.

12. Known myopathy.

13. History of another neoplastic disease except for curatively treated basal cellcarcinoma, squamous cell carcinoma of the skin, properly treated carcinoma in situof the uterine cervix or breast or superficial bladder tumors (Ta, Tis, or T1) thathave been successfully and curatively treated with no evidence of recurrent orresidual disease within three years prior to randomization. In case of priormalignancy, theInvestigator should ensure, based on histology or clinicalinformation, that the metastatic sites are sarcoma and not recurrence of theoriginal malignancy.

14. Limitation of the patient's ability to comply with the treatment or to follow-up theprotocol.

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