Pharmacokinetic Study of PM01183 in Combination With Irinotecan in Patients With Selected Solid Tumors

Inclusion Criteria:

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

- Age between 18 and 70 years (both inclusive).

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

- Life expectancy ≥ 3 months.

- No more than two prior lines of cytotoxic-containing chemotherapy regimens for
advanced disease. There is no limit for prior targeted therapy, hormonal therapy and
immunotherapy (such as nivolumab).

- Histologically or cytologically confirmed diagnosis of advanced disease of any of the
following tumor types:

1. Glioblastoma.

2. Soft-tissue sarcoma [excluding gastrointestinal stromal tumors (GIST)].

3. Endometrial carcinoma.

4. Epithelial ovarian carcinoma (including primary peritoneal disease and/or
fallopian tube carcinomas and/or endometrial adenocarcinomas) regardless of
platinum sensitivity.

5. Mesothelioma.

6. Gastroenteropancreatic neuroendocrine tumors (GEPNET).

7. Small cell lung cancer (SCLC).

8. Pancreatic adenocarcinoma.

9. Gastric carcinoma.

10. Colorectal carcinoma (CRC).

- Expansion phase: Tumor-specific cohort(s) at the RD:

1. Measurable disease according to Response Evaluation Criteria in Solid Tumors
(RECIST) v.1.1.

2. Documented disease progression per RECIST v.1.1 during or immediately after last
therapy according to any of the aforementioned criteria.

- At least three weeks since the last anticancer therapy, including investigational
drugs and radiotherapy, and at least six weeks since nitrosoureas and mitomycin
C(systemic).

- Adequate bone marrow, renal, hepatic, and metabolic function (assessed ≤ 7 days before
inclusion in the study):

1. Platelet count ≥ 100 × 109/L, hemoglobin ≥ 9.0 g/dL 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. Alkaline phosphatase (ALP) ≤ 2.5 × ULN (≤ 5 × ULN if disease-related/in the case
of liver metastases).

4. Total bilirubin ≤ 1.5 × ULN or direct bilirubin ≤ ULN.

5. International Normalized Ratio (INR) < 1.5 (except if patient is on oral
anticoagulation therapy).

6. Calculated creatinine clearance (CrCL) ≥ 30 mL/minute (using Cockcroft-Gault
formula).

7. Creatine phosphokinase (CPK) ≤ 2.5 × ULN.

8. Albumin ≥ 3.0 g/dL.

- Recovery to grade ≤ 1 or to baseline from any adverse event (AE) derived from previous
treatment (excluding alopecia and/or cutaneous toxicity and/or peripheral neuropathy
and/or fatigue grade ≤ 2).

Exclusion Criteria:

- Concomitant diseases/conditions:

1. History or presence of unstable angina, myocardial infarction, congestive heart
failure, or clinically significant valvular heart disease within the previous
year.

2. Symptomatic arrhythmia or any uncontrolled arrhythmia requiring ongoing
treatment.

3. Ongoing chronic alcohol consumption or cirrhosis with Child-Pugh score B or C.
Known Gilbert disease.

4. Active uncontrolled infection.

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

6. Myopathy or any clinical situation that causes significant and persistent
elevation of CPK (> 2.5 × ULN in two different determinations performed one week
apart).

7. Any past or present chronic inflammatory colon and/or liver disease, past
intestinal obstruction, pseudo or subocclusion or paralysis.

8. Evident symptomatic pulmonary fibrosis or interstitial pneumonitis, pleural or
cardiac effusion rapidly increasing and/or necessitating prompt local treatment
within seven days.

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

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

- Prior treatment with PM01183, trabectedin (Yondelis®) or topoisomerase I inhibitors
(irinotecan, topotecan, etc.).

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

- Known brain metastases or leptomeningeal disease involvement. Glioblastoma lesions
(primary or locally advanced) are eligible.

- Women who are pregnant or breast feeding and fertile patients (men and women) who are
not using an effective method of contraception. All patients (men and women) must
agree to use an effective method of contraception (if applicable) up to three months
after treatment discontinuation.