Clinical Trial of Lurbinectedin (PM01183)/Doxorubicin (DOX) Versus Cyclophosphamide (CTX), Doxorubicin (DOX) and Vincristine (VCR) (CAV) or Topotecan as Treatment in Patients With Small-Cell Lung Cancer

Inclusion Criteria:

1. Voluntary written informed consent

2. Adult patients ≥ 18 years

3. Histologically or cytologically confirmed diagnosis of limited or extensive stage SCLC
which failed one prior platinum-containing regimen and with a chemotherapy-free
interval (CTFI, time from the last dose of first-line chemotherapy to the occurrence
of progressive disease) ≥ 30 days. Small-cell carcinoma of unknown primary site with
or without neuroendocrine features confirmed in histology test(s) performed on
metastatic lesion(s) are eligible, if Ki-67/MIB-1 is expressed in >50% of tumor cells.

4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 2.

5. Adequate hematological, renal, metabolic and hepatic function within 7-10 days prior
to randomization

6. At least three weeks since last prior anticancer treatment and adequate recovery from
prior treatment toxicity

7. Prior radiotherapy (RT): At least four weeks since completion of whole-brain
irradiation, at least two weeks since completion of prophylactic cranial irradiation,
and to any other site.

8. Evidence of non-childbearing status for women of childbearing potential (WOCBP). WOCBP
must agree to use a highly effective contraceptive measure up to six weeks after
treatment discontinuation. Fertile male patients with WOCBP partners should use
condoms during treatment and for four months following the last investigational
medicinal product dose.

Exclusion Criteria:

1. More than one prior chemotherapy-containing line(re-challenge with the same initial
regimen is not allowed)

2. Patients who never received platinum-containing regimen for Small-cell Lung Cancer
(SCLC)

3. Prior treatment with PM01183, topotecan or anthracyclines.

4. Limited-stage patients who are candidates for local or regional therapy

5. Impending need for palliative RT or surgery for pathological fractures and/or for
medullary compression within four weeks prior to randomization.

6. Symptomatic or progressing or steroid requiring Central Nervous System (CNS)
involvement disease at least four weeks prior to randomization

7. Concomitant diseases/conditions:

Angina, myocardial infarction, congestive heart failure or clinically significant
valvular heart disease, arrhythmia, immunodeficiency (including known HIV
seropositive), ongoing or treatment-requiring chronic liver disease, active infection,
oxygen requirement within two weeks prior to randomization, diffuse interstitial lung
disease (ILD) or pulmonary fibrosis, second invasive malignancy treated with
chemotherapy and/or radiotherapy, invasive fungal infections requiring systemic
treatment within 12 weeks of randomization.

8. Pregnant or breast feeding women