Study of safety and efficacy of EGF816 in combination with INC280 in nonsmallcell lung cancer patients with EGFR mutatio
- Conditions
- non-small cell lung cancerMedDRA version: 21.1Level: 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-IT
- Lead Sponsor
- OVARTIS FARMA S.P.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 78
¿ 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 locally documented EGFR mutation L858R and/or ex19del, or a characterized de novo EGFR T790M mutation.
¿ Presence of at least one measurable lesion according to RECIST v.1.1
¿ ECOG performance status =2
¿ Patients must be screened for HBV. Patients who are either HBsAg positive or HBV-DNA positive must be willing and able to take antiviral
therapy 1-2 weeks prior to 1st dose of EGF816 treatment and continue on antiviral therapy for at least 4 weeks after the last dose of EGF816.
Additional management of the patients would be provided by a physician with expertise in management of HBV, if needed
¿ Patients must be screened for HCV. Patients must have negative hepatitis C antibody (HCV Ab) or are HCV Ab positive but with an undetectable level of HCV-RNA. Note: patients with detectable HCV-RNA are not eligible for the study
¿ Phase Ib: patients must have either an acceptable local result, detailing their c-MET and EGFR T790M status in a biopsy collected at or
post progression on the previous EGFR TKI therapy or sufficient tumor material available from a biopsy collected at or post progression on the
previous EGFR-TKI therapy for central assessment of c-MET and EGFRT790M. For Phase II Group 1, patients must have sufficient material available from a biopsy collected at or any time after progression on prior EGFR TKI for central assessment of c-MET and EGFRT790M. For Phase II Group 2, patients must have sufficient material collected at any time sent for central assessment of c-MET and EGFRT790M.
¿ 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).
¿ 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) and 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
Please refer to protocol for further details and/or additional inclusion criteria.
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: More than than one previous treatment with erlotinib, gefitinb, or afatinib, and/or previous treatment
with any investigational agent known to inhibit EGFR (mutant or wildtype)
¿ 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 EGFR monoclonal antibody therapy or dual TKI inhibitors.
¿ Previous treatment with a c-MET inhibitor or HGF-targeting therapy
¿ Patients with brain metastases
¿ History of another malignancy (Exception: Patients who have been disease-free for 3 years, or patients with a history of adequately treated
in-situ carcinoma of the uterine cervix, basal or squamous cell carcinoma, non-melanomatous cancer of skin, history of stage IA melanoma that has been cured, are eligible)
¿ Undergone a bone marrow or solid organ transplant
¿ Known history of human immunodeficiency virus (HIV) seropositivity (HIV testing is not mandatory)
¿ Patients receiving concomitant immunosuppressive agents or chronic
corticosteroids use at the time of study entry except for control of brain metastases, topical applications, inhaled sprays, eye drops or local
injections
¿ Patients wth clinically significant, uncontrolled cardiovascular disease
¿ Presence or history of interstitial lung disease or interstitial pneumonitis, including clinically signifiicant radiation pneumonitis significantly alter absorption of study treatment
¿ Patients have out of range laboratory values (as defined in the protocol)
Please refer to protocol for further details and/or additional exclusion criteria.
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;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;Primary end point(s): 1-Phase Ib part: Incidence of DLTs<br>2-Phase II part: Objective response rate (ORR) per RECIST v1.1;Timepoint(s) of evaluation of this end point: 1-First 28 days of treatment<br>2-Baseline, every 12 weeks
- Secondary Outcome Measures
Name Time Method