Phase I Study of Lurbinectedin (PM01183) in Combination With Paclitaxel, With or Without Bevacizumab, in Selected Advanced Solid Tumors

Clinical trial to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of
PM01183 in combination with weekly paclitaxel, with or without bevacizumab. Once a
recommended dose is defined for the PM01183 and weekly paclitaxel combination, the
feasibility of adding bevacizumab to this combination will be explored in a selected cohort
of patients to characterize the safety profile and feasibility of this combination, to obtain
preliminary information on antitumor activity, to obtain preliminary information on quality
of life (QoL), to characterize the pharmacokinetics (PK) of this combination and to detect
major drug-drug PK interactions and PK/PD (pharmacokinetic/pharmacodynamic) correlation and
to conduct an exploratory pharmacogenomic(PGx) analysis in patients with selected advanced
solid tumors.

Inclusion Criteria:

- Voluntarily signed and dated written informed consent

- Age between 18 and 75 years old (both inclusive)

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

- Life expectancy ≥ 3 months.

- Patients with a histologically/cytologically confirmed diagnosis of advanced and/or
unresectable disease of any of the following tumors:

1. Breast cancer

2. Epithelial ovarian cancer or gynecological cancer

3. Head and neck squamous cell carcinoma

4. Non-small cell lung cancer

5. Small cell lung cancer

6. Platinum-refractory germ-cell tumors.

7. Adenocarcinoma or carcinoma of unknown primary site

- Adequate bone marrow, renal, hepatic, and metabolic function

- Recovery to grade ≤ 1 or to baseline from any AE derived from previous treatment
(excluding alopecia of any grade).

- Pre-menopausal women must have a negative pregnancy test before study entry and agree
to use a medically acceptable method of contraception throughout the treatment period
and for at least six weeks after treatment discontinuation

Exclusion Criteria:

- Prior treatment with PM01183 or weekly paclitaxel or nanoalbumin-paclitaxel

- Patients who have previously discontinued paclitaxel-based regimes due to drug related
toxicity.

- Known hypersensitivity to bevacizumab or any component of its formulation

- Patients who have previously discontinued bevacizumab-containing regimes due to
drug-related toxicity.

- More than three prior lines of chemotherapy

- Less than three months since last taxane-containing therapy.

- Wash-out period:

1. Less than three weeks since the last chemotherapy-containing regimen

2. Less than three weeks since the last radiotherapy dose

3. Less than four weeks since last monoclonal antibody-containing therapy

- Concomitant diseases/conditions:

Unstable angina, myocardial infarction, valvular heart disease, encephalopathy, ischemic
attacks, hemorrhagic or ischemic cerebrovascular accident (CVA) or ongoing pulmonary
embolism within last year, arrhythmia, hepatopathy, uncontrolled infection, hemoptysis or
oxygen requiring dyspnea, known HIV infection, bleeding risk, muscular problems, peripheral
neuropathy, Symptomatic or progressive brain metastases or leptomeningeal disease.

- Men or pre-menopausal women who are not using an effective method of contraception as
previously described; actively breast feeding women.

- Patients who have pelvic irradiation with doses ≥ 45 Grays (Gy).

- History of previous bone marrow and/or stem cell transplantation.

- Confirmed bone marrow involvement