Rogaratinib in Patients With Advanced Pretreated Squamous-cell Non-small Cell Lung Cancer (SQCLC)

Inclusion Criteria

• •Written informed consent according to Swiss law and ICH-GCP regulations before registration and prior to any trial specific procedures including screening procedures. Informed consent for trial entry must be offered only after positive results of individual FGFR testing has been received.
• •Histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC (from inoperable stage IIIB to stage IV according to the 8th edition of the American Joint Commission on Cancer TNM staging system) with squamous-cell or predominantly squamous-cell histology (referred to SQCLC).
• •Archival or fresh tumor biopsy specimen for FGFR (subtypes 1-3) mRNA expression testing available. Acceptable samples include core needle biopsies for deep tumor tissue (minimum three cores) or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions.
• •High FGFR1-3 mRNA expression levels based on central analysis of archival or fresh tumor biopsy specimen (high expression defined as ≥ 1 FGFR isoform with RNAscope score of 3 or 4).
• •Measurable or evaluable disease (according to RECIST v1.1). Previously irradiated lesions should not be counted as target lesions unless there has been demonstrated progression in the lesion since radiotherapy before enrolment and no other lesions are available for selection as target lesions.
• •Patient failed standard systemic therapy for locally advanced or metastatic disease (1-3 prior chemotherapy regimens and at least 1 immune checkpoint inhibitor (combination allowed)).
• •Patients with known brain metastases must have undergone definitive treatment (surgery and/or radiation) at least 2 weeks prior to registration and must be clinically stable (no requirement of steroids and no worsening neurological deficits for 2 weeks prior registration).
• •Known human immunodeficiency virus (HIV)-infected patients who are healthy and have a low risk of AIDS-related outcomes are eligible, if,
• •* CD4+ T-cell counts are ≥ 350 cells/ųL
• •* No history of AIDS-defining opportunistic infection within past 12 months
• •* Patient agrees to concomitant antiretroviral therapy (ART) if not currently on ART, or is on ART for ˃ 4 weeks and has a HIV viral load ˂ 400 copies/mL.
• •Age ≥ 18 years.
• •WHO performance status 0-2.
• •Adequate bone marrow function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L1, platelet count ≥ 100 x 109/L2, hemoglobin ≥ 90 g/L2
• •1. without granulocyte colony-stimulating factor support within 2 weeks before the first administration of trial treatment
• •2. without transfusion or erythropoietin within 2 weeks before the first administration of trial treatment
• •Adequate hepatic function: total bilirubin ≤ 1.5 x ULN (≤ 3 x ULN for patients with known Gilbert syndrome), ALT and AST ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement of their cancer).
• •Adequate renal function: estimated glomerular filtration rate (eGFR) \> 30 mL/min/1.73m2 according to the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) abbreviated formula.
• •Adequate pancreatic function: lipase ≤ 2 x ULN.
• •Women with childbearing potential are using highly effective contraception, are not pregnant or lactating and agree not to become pregnant during trial treatment and during 5 months thereafter. A negative urine or serum pregnancy test before registration is required for all women with child-bearing potential.
• •Men agree not to donate sperm or father a child. Men without a vasectomy and with a partner of childbearing potential must agree to use condoms during trial treatment and during 5 months thereafter.
• •Patient is able and willing to swallow the trial IMP as whole tablet.
• •Patient consents to the mandatory translational research projects with biopsied tumor material.