LUX-Lung 8: A Phase III Trial of Afatinib (BIBW 2992) Versus Erlotinib for the Treatment of Squamous Cell Lung Cancer After at Least One Prior Platinum Based Chemotherapy

This randomised, open-label phase III trial will be performed in patients with advanced squamous cell carcinoma of the lung requiring second-line treatment after receiving first-line platinum-based chemotherapy. The primary objective of this trial is to compare the efficacy of BIBW 2992 to erlotinib as second-line treatment in this group of patients.

• Drug: afatinib
  Afatinib taken once daily, continuously until disease progression or unacceptable toxicity.
• Drug: erlotinib
  erlotinib taken once daily

• Experimental: Afatinib
  Patients receive afatinib tablets once daily
  Intervention: Drug: afatinib
• Active Comparator: Erlotinib
  Patients receive erlotinib tablets once daily
  Intervention: Drug: erlotinib

Inclusion criteria:

1. Diagnosis of advanced stage NSCLC squamous histology.
2. Platinum-based doublet chemotherapy as 1st line treatment of Stage IIIB/IV NSCLC.
3. Eligible to receive 2nd line therapy in the opinion of the investigator.
4. Measurable disease according to RECIST 1.1.
5. Adequate Performance Status.
6. Availability of tumour tissue material for correlative studies. Archived tumour tissue is acceptable.
7. Adequate organ function.
8. Age = 18 years and above.
9. Written informed consent that is consistent with ICH-GCP guidelines.

Exclusion criteria:

1. Prior treatment with EGFR directed small molecules or antibodies.
2. Radiotherapy within 4 weeks prior to randomization.
3. Active brain metastases .
4. Any other current malignancy or malignancy diagnosed within the past three (3) years (other than basal-cell carcinoma of the skin, in situ cervical cancer, in situ prostate cancer).
5. Known pre-existing interstitial lung disease.
6. Significant or recent acute gastrointestinal disorders with diarrhoea as a major symptom
7. Any other concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the test drug.
8. Women of child-bearing potential and men who are able to father a child, unwilling to be abstinent or use adequate contraception prior to study entry, for the duration of study participation and for at least 2 months after treatment has ended.

9. Female patients of childbearing potential (see Section 4.2.3.3) who:

   1. are nursing or
   2. are pregnant or
   3. are not using an acceptable method of birth control, or do not plan to continue using this method throughout the study and/or do not agree to submit to pregnancy testing required by this protocol.
10. Active hepatitis B infection (defined as presence of Hep B DNA), active hepatitis C infection (defined as presence of Hep C RNA) and/or known HIV carrier.
11. Known or suspected active drug or alcohol abuse in the opinion of the investigator.
12. Any contraindications for therapy with afatinib or erlotinib.
13. Known hypersensitivity to erlotinib, afatinib or the excipients of any of the trial drugs.
14. Major surgery within 4 weeks of starting study treatment.
15. Prior participation in an afatinib clinical study, even if not assigned to afatinib.
16. Use of any investigational drug within 4 weeks of randomisation (unless a longer time period is required by local regulations or by the guidelines for the investigational product).
17. Patients without Progression of their lung cancer.