A phase l/ll, multicenter, open-label study of EGFRmut-TKI EGF816 administered orally in adult patients with EGFRmut solid malignancies
- Conditions
- Advanced Non-small Cell Lung Cancer
- Registration Number
- JPRN-jRCT2080222568
- Lead Sponsor
- ovartis Pharma. K.K.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- completed
- Sex
- All
- Target Recruitment
- 211
Histologically or cytologically confirmed locally advanced (stage IIIB not amenable to definitive multi-modality therapy including surgery) or metastatic (stage IV) EGFR mutant NSCLC.
Patients with controlled brain metastases ECOG performance status: Phase I part: 0, 1, or 2; Phase II part: 0 or 1
Presence of at least one measurable lesion according to RECIST 1.1 per investigator assessment
Patients who are either Hepatitis B surface antigen (HBsAg) positive or hepatitis B virus (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 Patients must have negative hepatitis C antibody (HCV-Ab) or positive HCV-Ab but undetectable level of HCV-RNA. Note: patients with detectable HCV-RNA are not eligible for the study.
For Phase I: patients must have failed no more than 3 lines of any systemic antineoplastic therapy for advanced NSCLC, including EGFR-TKI
For Phase II: patients must be naive from any systemic antineoplastic therapy in the advanced setting. Patients who have failed no more than 1 cycle of systemic antineoplastic therapy in the advanced setting are allowed.
Patients with a history or presence of interstitial lung disease (ILD) or interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e. affecting activities of daily living or requiring therapeutic intervention)
Presence or history of another malignancy
Undergone a bone marrow or solid organ transplant
Known history of human immunodeficiency virus (HIV) seropositivity
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 with clinically significant, uncontrolled heart disease
Any prior therapies =< 4 weeks prior to the first dose of study treatment
Patients who are receiving treatment with medications that are known to be strong inhibitors or inducers of CYP3A4/5 and cannot be discontinued 1 week prior to the start of EGF816 treatment and for the duration of the study.
Patients who have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of EGF816
Patients who are receiving treatment with any enzyme-inducing anticonvulsant that cannot be discontinued at least 1 week before first dose of study treatment, and for the duration of the study
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception
Sexually active males unless they use a condom during intercourse while taking drug and for 3 months after stopping treatment
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1. Number of Participants With Dose Limiting Toxicities (DLTs) (Phase I Part) [ Time Frame: First 28 days of dosing ]<br>Number of participants with DLTs during the first 28 days of therapy. A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment with EGF816 and meets any of the criteria described in the protocol. A participant with multiple occurrences of DLTs under one treatment is counted only once.<br>2. Overall Response Rate (ORR) by Blinded Independent Review Committee (BIRC) (Phase II Part) [ Time Frame: From baseline up to 64 weeks ]<br>ORR is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) determined by BIRC assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
- Secondary Outcome Measures
Name Time Method