Inclusion Criteria:
* Voluntary written informed consent form (ICF) of the patient obtained before any study-specific procedure.
* Age ≥ 18 years of age; male or female.
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) score ≤1
* Histologically or cytologically confirmed gastrointestinal carcinoma
* Locally advanced unresectable or metastatic disease at study entry
* Known deleterious or suspected deleterious (or equivalent interpretation) mutations in DNA repair in ATM, ATR, CHEK2, BRCA1, BRCA2, RAD51, BRIP1, PALB2, PTEN, FANC, NBN, EMSY, MRE11, or ARID1A prior to study entry
* Progressive disease to prior treatment. Patients no longer able to continue prior treatment due to intolerable toxicity may be considered for study participation provided that radiology assessment confirms either stable disease or disease progression (i.e., no response to treatment).
* Measurable tumor lesions according to RECIST 1.1 criteria.
* Adequate hematological, renal, metabolic and hepatic function, defined as:
1. Hemoglobin ≥9 g/dL (patients may have received prior red blood cell \[RBC\] transfusion, if clinically indicated); absolute neutrophil count (ANC) ≥1.5 x 109/L, and platelet count ≥100 x 109/L.
2. Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤3.0 x upper limit of normal (ULN).
3. Total bilirubin ≤ ULN.
4. Albumin ≥3.0 g/dL.
5. Calculated creatinine clearance (CrCL) ≥30 mL/min (according to the Cockcroft and Gault´s formula).
* 11\. Washout periods prior to Day 1 of Cycle 1:
1. At least three weeks since last prior chemotherapy and/or investigational drugs.
2. At least four weeks since the last radiotherapy (RT) \> 30 Gy.
3. At least two weeks since the last palliative RT (≤ 10 fractions or ≤ 30 Gy total dose).
* Patients with prior malignancy successfully treated who are currently stable and on no active treatment are eligible.
* Recovery to grade ≤1 from any adverse event (AE) derived from previous anticancer treatment (excluding alopecia and/or skin toxicity of any grade and grade ≤2 peripheral neuropathy) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, v.5).
* Evidence of non-childbearing status for women of childbearing potential (WOCBP). WOCBP must agree to use a highly effective contraceptive measure\* during the trial and up to six weeks after treatment discontinuation, and fertile male patients with WOCBP partners must agree to refrain from fathering a child or donating sperm during the trial and up to four months after treatment discontinuation.
* Highly effective methods: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation; progestogen-only hormonal contraception associated with inhibition of ovulation; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomized partner; sexual abstinence
Exclusion Criteria:
* Prior treatment with lurbinectedin or trabectedin
* Neuroendocrine differentiation subtype in histology
* More than three prior systemic chemotherapy lines for advanced disease
* Known brain metastases or leptomeningeal disease involvement
* Concomitant diseases/conditions:
1. History of cardiac disease: myocardial infarction or symptomatic/uncontrolled angina within the year prior to enrollment; or pain history of left ventricular ejection fraction (LVEF) ≤ 50% assessed by multiple-gated acquisition scan (MUGA) or equivalent by ultrasound (US); or symptomatic arrhythmia.
2. Generalized edema, and/or ascites clinically evident or requiring drainages within three weeks prior to study entry. Permanent external drainages due to ascites are also excluded.
3. Immunocompromised patients, including those known to be infected by human immunodeficiency virus (HIV).
4. Known chronically active hepatitis B virus (HBV) or hepatitis C virus (HCV). 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.
5. Active uncontrolled infection.
6. Limitation of the patient's ability to comply with the treatment or to follow-up the protocol.
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.
* Patients acutely ill and/or in immediate vital distress, including those with rapidly deteriorating clinical condition or who may require unscheduled hospitalizations due to uncontrolled disease symptoms within the prior two weeks to treatment registration.
* Pregnant or breastfeeding women.
* Live vaccine administration within 3 weeks of study entry
