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

Phase 1

Conditions: Solid tumors
MedDRA version: 19.0Level: LLTClassification code 10049280Term: Solid tumourSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2013-004482-14-IT

Lead Sponsor: ovartis Pharma Services AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 500

Inclusion Criteria

For all patients (unless otherwise specified):
1. Written informed consent obtained prior to any screening procedures
2. Patient (male or female) = 18 years of age
3. Patients must have histologically or cytologically confirmed locally advanced (stage IIIB not amendable to definitive multi-modality therapy including surgery) or metastatic (stage IV) EGFR mutant NSCLC
4. Patients with controlled brain metastases may participate in the trial. They must complete any planned radiation therapy and/or surgery > 2 weeks prior to the first dose of study treatment and remain asymptomatic. Patients on steroids must have been on a stable low dose for 2 weeks prior to initiating study treatment.
5. ECOG performance status: Phase I part: 0, 1, or 2; Phase II part: 0 or 1
6. Presence of at least one measurable lesion according to RECIST 1.1 per Investigator assessment. A previously irradiated site lesion may be counted as a target lesion only if there is clear sign of progression since the irradiation (see Section 14.1 Appendix 1)
7. Patients must be screened for HBV. Patients who are either HBsAq positivie or HBVDNA positive must be willing 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.
8. Patients must be screened for HCV. 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 to enroll into the study.
9. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures
10. Requirement of EGFR mutation status and prior lines of treatment for Phase I patients- (Please see section 5.2 of the protocol for more details)
11. Requirements of EGFR mutation status and prior lines of treatment for Phase II patients:
• Group 1: Locally advanced or metastatic NSCLC with EGFR activating mutation (e.g. L858R and/or ex19del); Who have not received any systemic antineoplastic therapy, including EGFR TKI treatment, for advanced NSCLC; Note: patients who have received no more than 1 cycle of chemotherapy in the advanced setting are allowed.
• Group 2: Locally advanced or metastatic NSCLC with EGFR activating mutation (e.g. L858R and/or ex19del) and an acquired EGFR T790M mutation; Who have progressed on 1 and only 1 prior treatment with a 1st-generation EGFR TKI (e.g., erlotinib, gefitinib or icotinib) or 2nd-generation EGFR TKI (e.g., afatinib or dacomitinib); No more than 3 prior lines of systemic antineoplastic therapies (including EGFR TKI) in the advanced setting; 1st/2nd-generation EGFR TKI treatment must be the last prior treatment before study entry
• Group 3: Locally advanced or metastatic NSCLC with a de novo” EGFR T790M mutation; For purposes of this protocol, de novo” T790M will be defined as the presence of EGFR T790M mutation in NSCLC patients who have NOT been previously treated with any therapy known to inhibit EGFR; No more than 3 prior lines of systemic antineoplastic therapies in the advanced setting; No prior treatment with any therapy known to inhibit EGFR, including EGFR TKI
• Group 4: Locally advanced or metastatic NSCLC whose tumor harbors EGFR exon 20 insertion or deletion; No more than 3 prior lines of systemic antineoplastic therapies, including EGFR TKI, in the advanced setting
• Group 5: Locally advanced or metastatic NSCLC with EGFR activatin

Exclusion Criteria

For all patients (unless otherwise specified):
1. Patients with a history or presence of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e. affecting activities of daily living or requiring therapeutic intervention)
2. Patients with unstable brain metastases.
3. 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.
4. Undergone a bone marrow or solid organ transplant
5 Known history of human immunodeficiency virus (HIV) seropositivity (HIV testing is not mandatory)
6. 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
7. 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
8. Patients with out of range laboratory values defined as:
• Absolute Neutrophil Count (ANC) < 1.5 x 10^9/L
• Hemoglobin (Hgb) < 9 g/dL
• Platelets < 75 x 10^9/L
• Total bilirubin >1.5 x ULN. For patients with Gilbert’s syndrome total bilirubin >3.0 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3 x ULN for patients without hepatic metastasis. AST and/or ALT >5 x ULN for patients with hepatic metastasis
• Alkaline phosphatase (ALP) > 5 xULN
• Fasting plasma glucose > 175 mg/dL (> 9.8 mmol/L)
• Measured or calculated creatinine clearance < 45 mL/min
9. Patients with electrolytes outside the laboratory normal limits that cannot be corrected with supplements during screening:
• Potassium
• Magnesium
• Phosphorus
• Total calcium (corrected for serum albumin)
10. Patients 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.
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

Secondary Outcome Measures

Name	Time	Method

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