Clinical Study in Adult and Young Adult Patients With Advanced Desmoplastic Small Round Cell Tumor (DSRCT) ISG-TULIPS

Patients participating in this study have DSRCT that has spread locally or to other parts of the body and can no longer be surgically removed without causing significant harm. Treatment will continue until the tumor progresses further, severe side effects occur, or either patient or investigator decision. In addition, patients may participate in an optional biological study. The study will analyze the tumor's genes and the molecules related to them. By studying genes and their products, the investigators can better understand the behavior of the tumor and how the body responds to therapies.

Inclusion Criteria: 1. Histological centrally confirmed diagnosis of DSRCT with the documented presence of EWSR1-WT1 translocation. 2. Age ≥ 15 years. 3. Locally advanced (i.e. radical surgical resection of local disease unfeasible or surgery declined by the patient or surgery deemed to become less demolitive and / or easier after cytoreduction) and/or metastatic disease. 4. Measurable disease by RECIST v1.1. 5. Clinical or objective disease progression after the last administration of the last standard therapy, or have stopped standard therapy due to intolerability within 6 months from enrollment. 6. At least one prior chemotherapy based on anthracycline (considering chemotherapy administered for primary tumour) and no more than 3 prior chemotherapy lines. 7. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2. 8. Adequate bone marrow, renal, hepatic, and metabolic function (assessed ≤ 7 days before inclusion in the trial), defined as the following: 1. platelet count ≥ 100 × 109/L, hemoglobin ≥ 9.0 g/dL, white blood cells ≥ 3.0 × 109/L and absolute neutrophil count (ANC) ≥ 2.0 × 109/L, 2. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × the upper limit of normal (ULN), even in the presence of liver metastases, 3. total bilirubin ≤ 1.5 × ULN or direct bilirubin ≤ ULN, 4. International Normalized Ratio (INR) \< 1.5 (except if patient is on oral anticoagulation therapy), 5. calculated creatinine clearance (CrCL) ≥ 30 mL/minute (using Cockcroft-Gault formula), 6. creatine phosphokinase (CPK) ≤ 2.5 × ULN, 7. albumin ≥ 3.0 g/dL. 9. Cardiac ejection fraction ≥50% as measured by echocardiogram. 10. Recovery to grade ≤ 1 or to baseline from any adverse event (AE) derived from previous treatment (excluding alopecia and/or cutaneous toxicity and/or fatigue grade ≤ 2). 11. No history of arterial and/or venous thromboembolic event within the previous 12 months. 12. Females of childbearing potential must have a negative pregnancy test (preferable by serum or, if serum test unavailable, urine beta-HCG) within 7 days before treatment start. 13. Post-menopausal women must be amenorrhoeic for at least 12 months to be considered of non-childbearing potential. 14. Male and female patients of reproductive potential must agree to employ a highly effective method of birth control (Acceptable methods of contraception are described in Appendix 5) throughout the study and thereafter, at the end of study treatment, and for at least 7 months from the patient's last lurbinectedin administration in female patients of childbearing potential and for at least 4 months in men in fertile age after the last lurbinectedin administration. 15. The patient or legal representative must be able to read and understand the informed consent form (ICF) and must have been willing to give written informed consent and any locally required authorisation before any study-specific procedures, including screening evaluations, sampling, and analyses. Exclusion Criteria: 1. Prior treatment with lurbinectedin or trabectedin, Ecubectedin (PM 14) or PM54. 2. Known hypersensitivity to irinotecan or lurbinectedin or any of their components of the drugs products (excipients). 3. Other primary malignancy with \ 2.5 × ULN in two different determinations performed one week apart). 8. Severe and/or uncontrolled medical disease (i.e. uncontrolled diabetes, chronic renal disease, or active uncontrolled infection). 9. Known active brain metastasis. 10. Known chronic liver disease (i.e. chronic active hepatitis and cirrhosis). 11. Diagnosis of human deficiency virus (HIV), hepatitis C virus (HCV) infection or active hepatitis B (to be excluded during the screening period). 12. Any past or present chronic inflammatory colon and/or liver disease, past intestinal obstruction, pseudo or sub-occlusion or paralysis. 13. Evident symptomatic pulmonary fibrosis or interstitial pneumonitis, 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. 15. Known active COVID-19 disease (this includes positive test for SARS-CoV-2 in nasopharyngeal/oropharyngeal swabs or nasal swabs by PCR). 16. Prior bone marrow and/or stem cell transplantation, and allogenic transplant. 17. Last dose of systemic cytotoxic therapy or investigational therapy within 21 days from enrollment. 18. Prior treatment with any form of radiation therapy within 14 days from enrollment. 19. Major surgery within 3 weeks prior to study entry and minor surgery within 1 week prior to study entry. 20. Use of strong inducers of CYP3A activity within two weeks prior to the first infusion of lurbinectedin (Appendix 6). 21. Expected limitation of the patient's ability to comply with the treatment or follow-up protocol. 22. Subjects who have current active hepatic or biliary disease (with exception of patients with asymptomatic gallstones, liver metastasis or stable chronic liver disease per Investigator assessment). 23. Subjects who have known Gilbert's syndrome. 24. Patient has received a live or liver attenuated vaccines within 30 days before the first dose of study intervention. Killed vaccines are allowed.