| Eligibility |
Inclusion Criteria:
- Histologically or cytologically confirmed SCLC
- Extended disease according to the criteria of the Veteran's Administration - Lung
Cancer Group (VALG): disease extended beyond a hemithorax and the supraclavicular node
area. Pleural involvement will be considered as extended disease
- Assessment of adequate tissue availability for Program Cell Death-Ligand 1 (PD-L1)
immunohistochemistry testing
- Before patient registration, written informed consent must be given according to
International Conference of Harmonization-Good Clinical Practice (ICH-GCP), and
national/local regulations
- Tumor assessment performed within 10 days before randomization. Patient may or may not
have measurable disease
- Previous palliative brain radiotherapy is allowed if terminated at least 3 weeks
before randomization
- Partial or complete response according to RECIST (Response Evaluation Criteria in
Solid Tumors) 1.1 after 2 cycles of any platinum-based induction chemotherapy regimen
- Adequate hematopoietic, hepatic and renal function within 10 days before randomization
defined as follows:
- Absolute neutrophil count (ANC) = 1.5 x 10E9/L, Hemoglobin (Hb) = 9 g/dL and
platelet count = 100 x 10E9/L
- Serum creatinine clearance = 60 mL/min as calculated with Cockcroft-Gault formula
- Bilirubin = 1.5 x Upper Limit Normal (ULN), Alanine Aminotransferase (ALT) (SGTP)
and Aspartate Transaminase (AST) (SGOT) = 3 x ULN
- International Normalized Ratio (INR) or Prothrombin Time (PT) = 1.5 x ULN unless
subject is receiving anticoagulant therapy as long as PT or PTT is within
therapeutic range of intended use of anticoagulants
- Activated Partial Thromboplastin Time (aPTT) = 1.5 x ULN unless subject is
receiving anticoagulant therapy as long as a PTT is within therapeutic range of
intended use of anticoagulants N.B. Lactate Dehydrogenase (LDH) level assessment
is mandatory for randomization
- Women of child bearing potential (WOCBP) must have a negative urine or serum pregnancy
test within 72 hours before randomization
- Patients of childbearing / reproductive potential should use adequate birth control
measures, as defined by investigator, during the study treatment period and for at
least 120 days after the last study treatment. A highly effective method of birth
control is defined as those which result in low failure rate (i.e. less than 1% per
year) when used consistently and correctly.
- Female subjects who are breast feeding should discontinue nursing before randomization
and until 120 days after the last study treatment
Exclusion Criteria:
- Prior systemic therapy for SCLC; previous treatment with platinum and etoposide
concomitant with radiotherapy (RT) for limited disease is allowed if terminated at
least 1 year before patient randomization
- known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Patients with previously treated brain metastases may participate provided they are
stable (i.e. without evidence of progression by imaging and any neurologic symptoms
have returned to baseline), have no evidence of new or enlarging brain metastases, and
have not received steroids for at least 7 days before randomization
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 3-4 (at
registration) (patients who are judged by the investigator to be PS 2 due to primary
disease are the only PS 2 patients who are eligible)
- ECOG PS 2-4 (at randomization)
- Less than 3 month life expectancy
- History of interstitial lung disease (ILD) or a history of (non-infectious)
pneumonitis that required oral or IV steroids (other than Chronic Obstructive
Pulmonary Disease [COPD] exacerbation) or current pneumonitis or current evidence of
ILD
- Active autoimmune disease that has required systemic treatment in past 2 years (i.e.
with use of disease modifying agents, corticosteroids or immunosuppressive drugs), any
replacement therapy (i.e. thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment and is allowed
- Previous allogeneic tissue/solid organ transplant
- Active infection requiring therapy
- Known history of Human Immunodeficiency Virus (HIV) (known HIV 1/2 antibodies
positive). No known active Hepatitis B or C. Active Hepatitis B is defined as a known
positive HBsAg results. Active Hepatitis C is defined by a known positive Hep C Ab
result and known quantitative Hepatitis C Virus (HCV) RNA results greater than the
lower limits of detection of the assay
- Ongoing grade = 2 peripheral neuropathy
- Prior treatment with platinum, anti-PD-1, anti-PD-L1/2, anti interleukin-7
receptor-alpha (anti-CD127), Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) modulators
- Chronic use of immunosuppressive agents and/or systemic corticosteroids or any use in
the 3 days before randomization:
- Corticosteroid use on study for management of pembrolizumab Events of Clinical
Interest (ECIs), as pre-medication for the administration of chemotherapies, and/or a
pre-medication for contrast allergies/reactions is allowed
- Daily prednisone at doses of 5-7.5 mg is allowed as an example of replacement therapy.
Equivalent hydrocortisone doses are also permitted if administered as a replacement
therapy
- Prior use of live vaccines within 30 days before randomization. Examples of live
vaccines include, but are not limited to, the following : measles, mumps, rubella,
chicken pox, shingles, yellow fever, influenza A virus subtype (H1N1) flu, rabies,
Bacillus Calmette-Guerin (BCG), and typhoid vaccine
- Presence of any clinical, psychological, familial, sociological or geographical
condition potentially hampering compliance with the study protocol and follow-up
schedule; those conditions should be discussed with the patient before registration in
the trial
- Concurrent treatment with any investigational agent within 4 weeks before
randomization
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