Inclusion Criteria:

1. Voluntarily signed and dated written informed consent prior to any study specific
procedure.

2. Histologically confirmed DLPS by central review.

3. Metastatic or unresectable locally advanced disease

4. Progressive disease according to RECIST v1.1 criteria diagnosed on the basis of two
CT scan obtained at an interval less than 3 months and confirmed by central review

5. At least one prior anthracycline-containing chemotherapy regimen

6. Age ≥ 18 years.

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

8. Measurable disease according to RECIST v1.1 outside any previously irradiated field.

9. Adequate hematological, renal, metabolic and hepatic function.

1. Hemoglobin ≥ 9 g/dl (patients may have received prior red blood cell [RBC]
transfusion, if clinically indicated); absolute neutrophil count (ANC) ≥ 1.2 x
109/l, and platelet count ≥ 100 x 109/l.

2. Alkaline phosphatase (AP), alanine aminotransferase (ALT), and aspartate
aminotransferase (AST) 2.5 x upper limit of normality (ULN) (5 in case of
extensive skeletal involvement for AP exclusively).

3. Total bilirubin 1.5 x ULN.

4. Albumin > 25 g/l.

5. Calculated creatinine clearance (CrCl) ≥ 40 ml/min (according to cockroft and
Gault formula).

6. Creatine phosphokinase (CPK) ≤ 2.5 x ULN.

10. Troponin I ≤ ULN

11. No prior or concurrent malignant disease in the last 5 years except for adequately
treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in
situ transitional bladder cell carcinoma.

12. At least three weeks since last chemotherapy (six weeks in case of nitrosoureas and
mitomycin C), immunotherapy or any other pharmacological treatment and/or
radiotherapy.

13. Recovery to grade ≤ 1 from any adverse event (AE) derived from previous treatment
(excluding alopecia of any grade and non-painful peripheral neuropathy grade ≤ 2)
according to the National Cancer Institute Common Terminology Criteria for Adverse
Events (NCI-CTCAE, version 4.0).

14. Left ventricular ejection fraction (LVEF) by echocardiogram (ECHO) or multiple gated
acquisition (MUGA) within normal limits.

15. Women of childbearing potential must have a negative serum pregnancy test before
study entry. Both women and men must agree to use a medically acceptable method of
contraception throughout the treatment period and for six months after
discontinuation of treatment. Acceptable methods of contraception include
intrauterine device (IUD), oral contraceptive, subdermal implant and double barrier.

16. Patients with a french social security in compliance with the French law relating to
biomedical research

Exclusion Criteria:

1. Previous treatment with plitidepsin.

2. More than three prior lines of therapy for advanced disease.

3. Concomitant diseases/conditions:

1. History or presence of unstable angina, myocardial infarction, congestive heart
failure or clinically significant valvular heart disease. Symptomatic arrhythmia
or any arrhythmia requiring ongoing treatment, and/or prolonged QT-QTc grade >
1.

2. Previous mediastinal radiotherapy.

3. Previous treatment with anthracyclines at cumulative doses in excess of 450
mg/m2 doxorubicin equivalent.

4. Symptomatic arrhythmia or any arrhythmia requiring ongoing treatment, and/or
prolonged QT-QTc grade > 1.

5. Active uncontrolled infection.

6. Myopathy or persistent CPK elevations > 2.5 x ULN in two different
determinations performed with one week apart.

7. Any other major illness that, in the Investigator's judgment, will substantially
increase the risk associated with the patient's participation in this study.

4. Evidence of progressive or symptomatic central nervous system (CNS) or leptomeningeal
metastases.

5. Men or women of childbearing potential who are not using an effective method of
contraception as previously described; women who are pregnant or breast feeding.

6. Tumor tissue sample not available for pathological review and/or JNK immunochemistry
testing.

7. Participation in a clinical study and / or receipt of an investigational drug during
the last 30 days.

8. Previous enrolment in the present study.

9. Patient unable to follow and comply with the study procedures because of any
geographical, social or psychological reasons.

10. Known hypersensitivity to any involved study drug or any of its formulation
components