An international study of oral EGF816 in adult patients with EGFRmut Non Small Cell Lung Cancer (NSCLC)

Phase 1

• Conditions: Advanced Non-Small Cell Lung Cancer; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-003998-34-DE
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-05-02
• Last Update Posted: 20 August 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 410

Inclusion Criteria

1.Adult males or females = 18 years (for Japan only: = 20 years).
2.Written informed consent obtained prior to any screening procedures.
3.Histologically documented locally advanced or metastatic, stage IIIB/ IIIC (not candidates for definitive multi-modality therapy) or stage IV NSCLC with documented EGFR activating mutation (L858R or ex19del), assessed prior to screening by an accredited local laboratory or by a Novartis-designated central laboratory.
4.Mandatory provision of a formalin-fixed, paraffin embedded tumor tissue sample (archival tumor block or slides, or a newly obtained tumor sample) in a quantity sufficient to allow for retrospective analysis of EGFR mutation status for all the patients.
5.Treatment naïve from any systemic antineoplastic therapy in the advanced setting including chemotherapy, biologic therapy, immunotherapy or any investigational therapy.
6.Patients must have recovered from all toxicities related to prior (neo-) adjuvant systemic therapy to grade = 1 (CTCAE v 4.03)
7.Presence of at least one measurable lesion according to RECIST 1.1
8.Eastern Cooperative Oncology Group (ECOG) performance =1
9.Screened for HBV. Patients who are either HBsAg positive or HBV-DNA positive must be willing and able to take antiviral therapy at least 1 week prior to first dose of study treatment
10.Screened for HCV. Patients must have negative hepatitis C antibody (anti-HCV-Ab) or positive HCV-Ab but negative level of HCV-RNA
11.Meet the following laboratory values at the screening visit:
• Absolute Neutrophil Count =1.5 x 109/L
• Platelets =75 x 109/L
• Hemoglobin (Hgb) =9 g/dL
• Creatinine Clearance = 45 mL/min using Cockcroft-Gault formula
• Total bilirubin =1.5 x ULN
• Aspartate transaminase (AST) = 3.0 x ULN, except for patients with liver metastasis, who may only be included if AST =5.0 x ULN
• Alanine transaminase (ALT) = 3.0 x ULN, except for patients with liver metastasis, who may only be included if ALT =5.0 x ULN

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 205
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 205

Exclusion Criteria

1. Prior therapy with EGFR-TKI.
2. Known T790M positive mutation.
3. Any other known EGFR activating mutations other than L858R or ex19del. Patients whose tumors harbor other EGFR mutations concurrent with L858R or ex19del EGFR mutations are eligible.
4. Patients with symptomatic brain metastases are excluded. However, patients with asymptomatic and controlled brain metastases may participate in the trial
5. Patients with history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis
6. Any medical condition that would, in the investigator’s judgment, prevent the patient’s participation in the clinical study due to safety concerns, compliance with clinical study procedures or interpretation of study results
7. Presence or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years
8. Presence of clinically significant ophthalmologic abnormalities that might increase the risk of corneal epithelial injury, such as severe dry eye syndrome, keratoconjunctivitis sicca, Sjogren's syndrome, and severe exposure keratopathy
9. Bullous and exfoliative skin disorders at screening of any grade.
10. Presence or history of microangiopathic hemolytic anemia with thrombocytopenia.
11. Known history of testing positive for human immunodeficiency virus (HIV) infection, positive HIV test at screening if locally required.
12. Cardiac or cardiac repolarization abnormality
13. Major surgery: =4 weeks to starting study treatment or who have not recovered from side effects of such procedure.
14. Unable or unwilling to swallow tablets or capsules
15. Patients who are receiving treatment with following medications and cannot be discontinued 1 week prior to the start of study treatment and for the duration of the study.
• Strong CYP3A4/5 inhibitors
• Strong and moderate CYP3A4/5 inducers
16. Patients who have impairment of GI function or GI disease that may significantly alter the absorption of study treatment (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome)
17. Pregnant or nursing (lactating) women
18. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and 3 months of after stopping study medication
19. Sexually active males unless they use a condom during intercourse while taking the drug during treatment, and for 3 months after stopping study treatment and should not father a child in this period.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified