Study of safety and efficacy of EGF816 in combination with INC280 in non-small cell lung cancer patients with EGFR mutatio
- Conditions
- non-small cell lung cancerMedDRA version: 17.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-000726-37-FR
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 78
?Patients (male or female) = 18 years of age.
? Patients with histologically documented, locally advanced or recurrent (stage IIIB who are not eligible for combined modality treatment) or metastatic (Stage IV) non-small cell lung cancer.
? Patients must have EGFR mutation L858R and/or ex19del.
? Presence of at least one measurable lesion according to RECIST v.1.1
? ECOG performance status =2
? Phase Ib only: documented progression of disease according to RECIST v1.1 while on continuous treatment with EGFR TKI (e.g. erlotinib, gefitinib or afatinib, other EGFR TKIs may be allowed after discussion with Novartis).
? Phase II Group 1 only: Patients with acquired resistance to EGFR TKI treatment defined as documented clinical benefit (CR (any duration), PR (any duration), or SD for at least 6 months) on prior EGFR TKI therapy (e.g. erlotinib, gefitinib or afatinib, other EGFR TKIs may be allowed after discussion with Novartis) who subsequently demonstrated progression according to RECIST v1.1.
? Phase II Group 2 only: Advanced NSCLC patients who have not been previously treated with any therapy known to inhibit EGFR and harbor de novo T790M mutation
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 55
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 23
? Phase Ib and Phase II Group 1 only: Patients who have received more than one prior line of EGFR TKI therapy
? Phase Ib and Phase II Group 1 only: Patients who have received more than three prior lines of antineoplastic therapy (including EGFR TKI) in the advanced setting.
? Phase II Group 2 only: Patients who have received more than two previous lines of antineoplastic therapies in advance setting.
? Phase II Group 2 only: Previous treatment with an investigational or marketed agent that inhibits EGFR. EGFR inhibitors include (but not limited to) erlotinib, gefitinib or other anti-EGFR or EGF monoclonal antibody therapy or dual TKI inhibitors.
? Previous treatment with a c-MET inhibitor or HGF-targeting therapy.
? Patients with brain metastases.
? Patients have out of range laboratory values defined as
? Absolute Neutrophil Count (ANC) <1.5 x 109/L
? Hemoglobin (Hb) <9 g/dL
? Platelets (PLT) <100 x 109/L
? Total bilirubin >1.5 x upper limit of normal (ULN). For patients with Gilbert’s syndrome total bilirubin >2.5 x ULN.
? AST and/or ALT >3 x ULN
? Patients with tumor involvement of the liver must have AST and/or ALT >5 x ULN
? Serum creatinine >1.5 x ULN
? Measured or calculated creatinine clearance =45mL/min
? Asymptomatic serum amylase and lipase > Grade 2
? Serum amylase or serum lipase CTCAE grade = 1 with signs and/or symptoms suggesting pancreatitis or pancreatic injury
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Phase Ib part: To estimate the MTD or RP2D of EGF816 in combination with INC280 <br>Phase II part: To estimate the preliminary anti-tumor activity of EGF816 in combination with INC280<br>;Secondary Objective: To characterize the safety, tolerability and pharmacokinetics of EGF816 in combination with INC280<br>To evaluate the preliminary anti-tumor activity of EGF816 in combination with INC280<br>;Primary end point(s): 1-Phase Ib part: Incidence of DLTs<br>2-Phase II part: Objective response rate (ORR) per RECIST v1.1<br>;Timepoint(s) of evaluation of this end point: 1-First 28 days of treatment<br>2-Baseline, every 12 weeks <br>
- Secondary Outcome Measures
Name Time Method