PM14 Administered Intravenously to Patients with Advanced Solid Tumors

Inclusion Criteria:

1. Voluntarily signed and dated written informed consent (IC), obtained prior to anyspecific study procedure.

2. Age ≥18 years.

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

4. For the Dose escalation phase: Patients with pathologically confirmed diagnosis of advanced solid tumors for whomno curative standard therapy exists. For the Expansion phase: Patients with pathologically confirmed diagnosis of one of the followingmalignancies, for whom the standard of care therapies have failed, or are intolerantto standard of care therapies that are known to provide clinical benefit:

5. Gastrointestinal tumors: colorectal cancer, gastric cancer.

6. Sarcomas: liposarcoma, leiomyosarcoma, synovial sarcoma, Ewing's sarcoma.

7. Tumors with deleterious germline BRCA mutation: epithelial ovarian cancer (including primary peritoneal and fallopian tube cancer), breast cancer,pancreatic cancer, prostate cancer, or any other malignancies.

8. Epithelial ovarian cancer (including primary peritoneal and fallopian tubecancer) with no deleterious germline BRCA mutations or with unknown BRCAstatus.

9. Adrenocortical carcinoma.

10. Patients included in the Expansion phase need to meet the following requirementsregarding the maximum number of prior chemotherapy regimens (no limit for biologicaltherapies):

11. Gastrointestinal tumors: no more than three prior chemotherapy lines forcolorectal cancer; and no more than two prior chemotherapy lines for gastriccancer.

12. Sarcomas: no more than two prior chemotherapy lines for liposarcoma,leiomyosarcoma and synovial sarcoma; and no more than three prior chemotherapylines for Ewing's sarcoma.

13. Tumors with deleterious germline BRCA mutation: no more than three priorchemotherapy lines for breast cancer; and no more than two prior chemotherapylines for prostate cancer, ovarian cancer, pancreatic cancer, gastriccarcinoma, or any other malignancies.

14. Epithelial ovarian cancer with unknown BRCA status or no deleterious germlineBRCA mutations: no more than three prior chemotherapy lines.

15. Adrenocortical cancer: no more than one prior chemotherapy line (excludingmitotane as single agent or associated with no chemotherapeutic agents). Note: for the purpose of this criterion, the following situations will be consideredas one chemotherapy line:

• Adjuvant chemotherapy; neoadjuvant chemotherapy; both adjuvant and neoadjuvantchemotherapy (except if time to relapse was >12 months, in which case it willnot be considered as one line); and

• Change of chemotherapy due to reasons other than PD, such as toxicity (in thiscase, the two lines will count as a single line).

6. Life expectancy ≥3 months.

7. Patients with measurable or non-measurable disease according to the RECIST v.1.1 areeligible during the dose escalation phase.

8. Patients included in the Expansion phase must have:

9. Measurable disease according to the RECIST v.1.1 and/or evaluable disease byserum markers in case of prostate and ovarian cancer (according to the PSAWGRand the GCIG specific criteria, respectively).

10. Confirmed progressive disease after last therapy at study entry.

11. Recovery to grade ≤1 from drug-related AEs of previous treatments, excludingalopecia and grade 1/2 asthenia or fatigue, according to the NCI-CTCAE v.4.

12. Laboratory values within seven days prior to first infusion:

13. ANC ≥1.5 x 10^9/L, platelet count ≥100 x 10^9/L and hemoglobin ≥9 g/dL (patients may be transfused for anemia as clinically indicated prior to studyentry).

14. AST and ALT ≤3.0 x ULN.

15. Total bilirubin ≤ULN (up to 1.5 x ULN for patients with Gilbert's syndrome).

16. Creatinine clearance ≥30 mL/min (calculated using the Cockcroft and Gault'sformula).

17. Serum albumin ≥3 g/dL.

18. Wash-out periods:

19. At least three weeks since the last chemotherapy (six weeks if therapy includednitrosoureas or systemic mitomycin C).

20. At least four weeks since the last monoclonal antibody (MAb)-containing therapyor curative radiotherapy (RT).

21. At least two weeks since the last biological/investigational single-agenttherapy (excluding MAbs) and/or palliative RT (≤10 fractions or ≤30 Gy totaldose).

22. In patients with hormone-sensitive breast cancer progressing while on hormonetherapy (except for luteinizing hormone-releasing hormone (LHRH) analogues inpre-menopausal women or megestrol acetate), all other hormonal therapies mustbe stopped at least one week before study treatment start.

23. Castrate-resistant prostate cancer (CRPC) patients may continue receivinghormone therapy prior to and during study treatment.

Exclusion Criteria:

1. Concomitant diseases/conditions:

2. Increased cardiac risk:

• Uncontrolled arterial hypertension despite optimal management (≥160/100mmHg).
• Presence of clinically relevant valvular disease.
• History of long QT syndrome.
• Corrected QT interval (QTcF, Fridericia correction) ≥450 msec on screeningelectrocardiogram (ECG).
• History of ischemic heart disease, including myocardial infarction,angina, coronary arteriography or cardiac stress testing with findingsconsistent with coronary occlusion or infarction ≤6 months prior to studyentry.
• History of heart failure or left ventricular dysfunction (left ventricularejection fraction [LVEF] below normal values) by multiple-gatedacquisition scan (MUGA) or echocardiography (ECHO).
• ECG abnormalities, including any of the following: left bundle branchblock, right bundle branch block with left anterior hemiblock, second (Mobitz II) or third degree atrioventricular block.
• Symptomatic arrhythmia (excluding anemia-related sinusal tachycardia grade ≤2) or any arrhythmia requiring ongoing treatment, and/or prolonged QT-QTcgrade ≥2; or presence of unstable atrial fibrillation. Patients withstable atrial fibrillation on treatment are allowed provided they do notmeet any other cardiac or prohibited drug exclusion criterion.
• Clinically significant resting bradycardia (<50 beats per minute).
• Concomitant medication with risk of inducing torsades de pointes, whichcannot be discontinued or switched to an alternative drug prior to startPM14 dosing.
• Use of a cardiac pacemaker.

2. Active infection requiring systemic treatment.

3. Known human immunodeficiency virus (HIV) or known hepatitis C virus (HCV)infection or active hepatitis B.

4. Any other major illness that, in the Investigator's judgment, willsubstantially increase the risk associated with the patient's participation inthis study (e.g., COVID-19).

5. Symptomatic, high dose steroid-requiring, and progressing central nervous system (CNS) disease. Exceptions will be made for (i) patients who have completedradiotherapy at least four weeks prior to inclusion (asymptomatic, non-progressingpatients taking steroids in the process of already being tapered within two weeksprior to inclusion), and (ii) patients with asymptomatic brain metastasis withoutneed for radiotherapy or steroids.

6. Patients with carcinomatous meningitis regardless of clinical stability.

7. Prior bone marrow or stem cell transplantation, or radiation therapy in more than 35% of bone marrow.

8. Prior treatment with trabectedin or Lurbinectedin (PM01183) within six months priorto onset of study treatment.

9. Use of (strong or moderate) inhibitors or strong inducers of CYP3A4 activity withintwo weeks prior to the first infusion of PM14.

10. Known hypersensitivity to any of the components of the drug product

11. Limitation of the patient's ability to comply with the treatment or to follow theprotocol procedures.

12. Pregnant or lactating women. Women of childbearing potential (WOCBP) must agree touse an effective contraception method to avoid pregnancy during trial treatment andfor at least six months after the last infusion. Fertile male patients must agree torefrain from fathering a child or donating sperm and to use an effectivecontraception method during treatment and for four months after the last infusion.WOCBP who are partners of fertile male patients must use an effective contraceptionmethod during the patients' treatment and for four months after the last infusion.