An interventional study of oral EGF816 in adult patients with EGFRmut solid malignancies

Conditions: Solid tumors
MedDRA version: 18.0Level: LLTClassification code 10049280Term: Solid tumourSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2013-004482-14-FR

Lead Sponsor: ovartis Pharma AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 211

Inclusion Criteria

- Written informed consent must be obtained prior to any screening procedures
- Additionally for Phase I:
- Patients must have NSCLC harboring with any documented EGFR T790M mutation
Additionally for Phase II :
- Group 1: patients must have advanced NSCLC with EGFR mutation (L858R or ex19del, not T790M)
- Group 2: patients must have advanced NSCLC with an acquired T790M EGFR mutation
- Group 3: patients must have advanced NSCLC with a de novo T790M EGFR mutation.
- Group 4: patients must have an advanced solid tumor harboring any EGFR mutation and NOT be otherwise eligible for groups 1-3
- ECOG performance status = 2
- Presence of at least one measurable lesion according to RECIST v1.1
Other protocol-defined inclusion criteria may apply
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 72
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 139

Exclusion Criteria

Phase I part only:
- Patient have received more than 3 previous anti-neoplastic therapies in the advanced setting
Phase II part only:
- Group 1: No limitation of previous anti-neoplastic treatments in the advanced setting
- Group 2: More than total of 2 previous anti-neoplastic therapies in theadvanced setting
- Group 3: More than total of 2 previous anti-neoplastic therapies in the advanced setting
- Group 4: No limitation of previous anti-neoplastic treatments in the advanced setting
- Patients with brain metastases
- Any medical condition that would, in the investigator's judgment,prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures
- Patient have out of range laboratory values defined as:
• Bone marrow function
• Absolute Neutrophil Count (ANC) <1.5 x 10^9/L
• Hemoglobin (Hgb) <9 g/dL
• Platelets <100 x 10^9/L
• Hepatic and renal function
• Total bilirubin >1.5 x upper limit of normal (ULN). For patients with Gilbert's syndrome total bilirubin >2.5 x upper limit of normal (ULN).
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3 x ULN
- Patients with tumor involvement of the liver have AST and/or ALT >5 x ULN
• Serum creatinine >1.5 x ULN and/or measured creatinine clearance <75% LLN - Patients receiving treatment with medications that are known to be 1) strong inhibitors or inducers of CYP3A4/5; 2) CYP2D6 substrate with narrow therapeutic index
Other protocol-defined exclusion criteria may apply

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Phase I part: To estimate the MTD or RDE of EGF816<br>Phase II part: To investigate the anti-tumor activity of EGF816;Secondary Objective: Phase I/II:<br>1. To characterize the safety and tolerability of EGF816<br>2. To further investigate the anti-tumor activity of EGF816<br>3. To characterize the PK properties of EGF816 and metabolite LMI258<br>4. To assess the tumor EGFR signaling inhibition by EGF816;Primary end point(s): Phase I part: Incidence of dose limiting toxicity (DLT)<br>Phase II part: Objective response rate (ORR);Timepoint(s) of evaluation of this end point: Phase I part: first 28 days of dosing<br>Phase II part: baseline, every 8 weeks until disease progression,consent withdraw or death up to 3 years

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Phase I/II:<br>1. Frequency/severity of adverse events (AEs), serious adverse events<br>(SAEs) , Number of Dose interruptions and reductions<br>2. Best overall response (BOR), Progression-free survival (PFS) and Duration of response (DOR)<br>3. Plasma concentration vs. time profiles, plasma PK parameters<br>4. Pre- and post- treatment immunohistochemistry of EGFR pathway molecules;Timepoint(s) of evaluation of this end point: Phase I/II:<br>1. continuously throughout the study until 30 days after safety follow up<br>2. baseline, every 8 weeks until disease progression, consent withdraw or death up to 3 years<br>3. cycle 1 day 1,2,8, 15; cycle 2 day 1, 2; cycle 3 day 1; cycle 4 day 1<br>4. baseline and cycle 1 day 15

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