Testing Afatinib in Combination With Pembrolizumab in Patients With Squamous Cell Carcinoma of the Lung

Inclusion Criteria:

- Pathologically confirmed diagnosis of NSCLC considered to be of squamous histology,
including mixed histology, in the opinion of the investigator.

- Locally advanced (stage IIIb) or metastatic (stage IV) NSCLC not considered eligible
for curative therapy.

- Documented disease progression or relapse (based on investigator's assessment) during
or after completion of at least 2 cycles of platinum-based chemotherapy as first line
treatment of Stage IIIB/IV SCC of the lung. This includes patients relapsing within 6
months of completing (neo)adjuvant/curative-intent chemotherapy or definitive
chemoradiotherapy. Patients should be eligible to receive 2nd line therapy in the
opinion of the investigator.

- At least one target lesion (outside the brain) that can be accurately measured per
Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. In patients who
only have one target lesion and a biopsy of the lesion is required; the baseline
imaging must be performed at least two weeks after the biopsy.

- Availability and willingness to provide a fresh tumour tissue sample obtained after
relapse or progression on or after prior therapy. In case a fresh biopsy cannot be
obtained (e.g. inaccessible lesions or patient safety concern), an archived specimen
may be submitted.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

- Adequate organ function (all screening labs should be performed within 10 days prior
to treatment initiation).

- Recovery from major surgery or any previous anti-cancer or radiation therapy-related
toxicity to ≤ CTCAE Grade 1 at C1_V1 (except for alopecia; stable sensory neuropathy
must be ≤ CTCAE Grade 2).

- At least 18 years of age or over the legal age of consent in countries where that is
greater than 18 years at screening.

- Signed and dated written informed consent in accordance with ICHGCP and local
legislation prior to admission to the trial.

- Male or female patients. Women of childbearing potential (WOCBP) and men able to
father a child must be ready and able to use highly effective methods of birth control
per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used
consistently and correctly, starting with the screening visit and through 120 days
after the last dose of pembrolizumab treatment and 2 weeks after last afatinib
treatment, respectively, as listed in the protocol. A list of contraception methods
meeting these criteria is provided in the patient information. -- Note: Female
patients of childbearing potential must have a negative urine or serum pregnancy test
within 72 hours prior to taking study medication. If the urine test is positive or
cannot be confirmed as negative, a serum pregnancy test will be required. The serum
pregnancy test must be negative for the patient to be eligible.

Exclusion criteria:

- Prior therapy with any immune checkpoint inhibitor; however, prior (neo) adjuvant
checkpoint inhibitor therapy is allowed if completed at least 12 months before
relapse.

- Prior therapy with EGFR inhibiting drugs; however, prior EGFR-targeted (neo) adjuvant
therapy is allowed if completed at least 12 months before relapse.

- Treatment with prior chemotherapy, non-EGFR targeted therapy, or anti-cancer hormonal
treatment within 2 weeks prior to the first dose of trial treatment.

- Current or previous treatment with experimental therapy or use of an investigational
device within 30 days prior to the first dose of trial treatment.

- Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to the first dose of
trial treatment.

- Received a live vaccine within 30 days prior to the first dose of trial treatment.
Seasonal flu vaccines that do not contain live virus are permitted.

- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other
form of immunosuppressive therapy within 7 days prior to the first dose of trial
treatment. The use of physiologic doses of corticosteroids is allowed.

- Any history of or concomitant condition that, in the opinion of the investigator,
would compromise the patient's ability to comply with the trial or interfere with the
evaluation of the efficacy and safety of the test drugs.

- Radiotherapy within 4 weeks prior to start of treatment except as follows:

- Palliative radiotherapy to regions other than the chest is allowed up to 2 weeks
prior to start of treatment;

- Single dose palliative radiotherapy for symptomatic metastasis within 2 weeks
prior to start of treatment may be allowed but must be agreed with the Sponsor.

- Major surgery (according to the investigator's assessment) performed within 4 weeks
prior to start of treatment or planned during the projected course of the study.

- Requirement or wish to continue the intake of restricted medications (see Section
4.2.2.1) or any drug considered likely to interfere with the safe conduct of the
trial.

- Known history of hypersensitivity to afatinib or any of its excipients.

- Known history of hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its
excipients.

- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.

-- Note: Patients with previously treated brain metastases may participate provided
they are stable without evidence of progression by imaging (using the identical
imaging modality for each assessment, either MRI or CT scan) for at least four weeks
prior to the first dose of trial treatment and any neurologic symptoms have returned
to baseline), have no evidence of new or enlarging brain metastases, and are not using
steroids for at least 7 days prior to trial treatment. This exception does not include
carcinomatous meningitis which is excluded regardless of clinical stability.

- Active autoimmune disease that has required systemic treatment in past 2 years (i.e.
with use of disease modifying agents, systemic corticosteroids or immunosuppressive
drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.

- History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required
steroids or current ILD/pneumonitis.

- Any history or presence of uncontrolled gastrointestinal disorders that could affect
the intake and/or absorption of the study drug (e.g. nausea, vomiting, Crohn's
disease, ulcerative colitis, chronic diarrhoea, malabsorption) in the opinion of the
investigator.

- Active infectious disease requiring intravenous systemic therapy or which puts the
patient at increased risk in the opinion of the investigator.

- Previous or concomitant malignancies at other sites than the lung, except:

- Effectively treated non-melanoma skin cancers;

- Effectively treated carcinoma in situ of the cervix;

- Effectively treated ductal carcinoma in situ;

- Other effectively treated malignancy that has been in remission for more than 3
years and is considered to be cured.

- Known human immunodeficiency virus (HIV) (HIV 1/2 antibodies), active hepatitis B
(e.g. HBsAg reactive) or hepatitis C (e.g. HCV RNA [qualitative] is detected).

- History of active TB (Bacillus Tuberculosis).

- History or presence of cardiovascular abnormalities such as uncontrolled hypertension,
congestive heart failure New York Heart Association (NYHA) classification of ≥3,
unstable angina or poorly controlled arrhythmia which are considered as clinically
relevant by the investigator. Myocardial infarction within 6 months prior to start of
treatment.

- Psychiatric, substance abuse disorders, or chronic alcohol abuse or any condition as
per investigator's opinion.

- Further criteria apply, some were shortened.