A Clinical Study in Three-arm of Lurbinectedin (PM01183) Alone or in Combination With Gemcitabine and a Control Arm With Docetaxel as Second Line Treatment in Non-Small Cell Lung Cancer (NSCLC) Patients

A randomized-controlled, three-arm, phase II study of lurbinectedin (PM01183) alone or in
combination with gemcitabine and a control arm with docetaxel as second-line treatment in
unresectable non-small cell lung cancer (NSCLC)patients to evaluate the antitumor activity
as progression-free survival at four months (PFS4) of PM01183 alone or in combination with
gemcitabine as using single agent docetaxel as a reference in the control arm as current
standard of care and to analyze overall survival (OS), overall survival rate at 1-year
(OS12), duration of response (DR), antitumor activity, as response rate (RR), safety and
efficacy profiles of PM01183 alone and in combination with gemcitabine, to be preliminary
compared with docetaxel, patients' quality of life (QoL), pharmacokinetics (PK) of PM01183,
pharmacokinetic/pharmacodynamic (PK/PD)correlation and pharmacogenomics (PGx)to explore
potential correlations between clinical outcomes and molecular parameters found in tumor and
blood samples

Inclusion Criteria:

- Histologically or cytologically confirmed unresectable NSCLC

- Patients must have failed one prior line of CT-based therapy for unresectable disease

- Age between 18 and 75 years

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

- Adequate hematological, renal, metabolic and hepatic function

- At least three weeks since the last prior therapy, at least four weeks since
completion of any prior radiotherapy

- Negative pregnancy test for pre-menopausal women

Exclusion Criteria:

- Concomitant diseases/conditions as unstable angina, myocardial infarction,
symptomatic congestive heart failure or asymptomatic with left ventricular ejection
fraction (LVEF) ≤ 50%, dyspnea, infection by human immunodeficiency virus (HIV),
active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, active
uncontrolled infection, pleural or pericardial effusions, myopathy, limitation of the
patient's ability to comply with the treatment or to follow-up the protocol, any
other major illness

- Histological features of neuroendocrine or bronchioalveolar differentiation.

- Unknown epidermal growth factor receptor (EGFR)mutation status or previously known
EGFR mutated status in patients with adenocarcinoma.

- Prior or concurrent invasive malignant disease, unless in complete remission for more
than three years.

- Significant cancer-related weight loss (≥10%)within four weeks prior to treatment
start

- Prior treatment with docetaxel-containing therapy

- Symptomatic, steroid-requiring or progressive central nervous system (CNS)
involvement

- Paraneoplastic syndromes