Histological or cytological proof of advanced NSCLC; for PART B: treated with first line therapy for metastatic disease only.
Written documentation of a known pathogenic KRAS (exon 2, 3 or 4) mutation and PIK3CA wildtype (defined as absence of mutations in exon 9 and 20)
Able and willing to give written informed consent
Able and willing to undergo blood sampling for PK and PD analysis
Life expectancy \>=3 months allowing adequate follow up of toxicity evaluation and antitumor activity.
WHO performance status of 0 or 1.
Able and willing to undergo a tumor biopsies prior to start, after two weeks (part A only) and upon progression of disease
Measurable disease according to RECIST 1.1
Adequate organ system function measured by laboratory values
You may not be if
Any treatment with investigational drugs within 30 days prior to receiving the first dose of investigational treatment.
History of another malignancy Exception PART A: Patients who have been disease-free for at least 3 years, or patients with a history of completely resected non-melanoma skin cancer and/or patients with indolent second malignancies are eligible. Exception PART B: Adequately treated carcinoma in situ of the cervix and adequately treated basal cell carcinoma of the skin. 3. Symptomatic or untreated leptomeningeal disease.
Symptomatic brain metastasis.
Patients previously treated with any drug combination known to interfere with EGFR, HER2, HER3, HER4 or MAPK- and PI3K-pathway components, including inhibitors of PTEN, PI3K, AKT, mTOR, BRAF, MEK and ERK.
History of interstitial lung disease or pneumonitis
Radio-, immuno- or chemotherapy within the last 2 weeks prior to receiving the first dose of investigational treatment. Palliative radiation (1x 8Gy) is allowed.
Opthalmological diseases
Patients with left ventricular ejection fraction (LVEF) \< 55%
Patients with cardiac comorbidities
Concomitant or recent use (in the past 14 days) of strong inhibitors and inducers of CYP1A2, CYP2C19, CYP3A4, 3A5 and P-glycoprotein (P-gp)
Clareo Health | Afatinib and Selumetinib in Advanced KRAS Mutant and PIK3CA Wildtype Non-small Cell Lung Cancer
