Study of safety and efficacy of EGF816 in combination with INC280 in non-small cell lung cancer patients with EGFR mutation

• Register: EUCTR
• Last refreshed on: 18 January 2021
• Main ID: EUCTR2014-000726-37-FR
• Date of registration: 07/01/2015
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Study of safety and efficacy of EGF816 in combination with INC280 in non-small cell lung cancer patients with EGFR mutation
• Scientific title: A phase Ib/II, multicenter, open-label study of EGF816 in combination with INC280 in adult patients with EGFR mutated non-small cell lung cancer
• Date of first enrolment: 29/01/2015
• Target sample size: 78
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000726-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Canada, France, Germany, Hong Kong, Italy, Korea, Republic of, Norway, Singapore, Spain, Taiwan, United States

Contacts

• Name: Information&Communication Médicale
• Affiliation: Novartis Pharma S.A.S.

• Name: Information&Communication Médicale
• Affiliation: Novartis Pharma S.A.S.

Key inclusion & exclusion criteria

Inclusion criteria:
?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

Exclusion criteria:
? 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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

non-small cell lung cancer
MedDRA version: 17.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Code: INC280
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Not available
CAS Number: 1197376-85-4
Current Sponsor code: INC280
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Product Code: INC280
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Not available
CAS Number: 1197376-85-4
Current Sponsor code: INC280
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Product Code: EGF816
Pharmaceutical Form: Capsule
Current Sponsor code: EGF816
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Product Code: EGF816
Pharmaceutical Form: Capsule
Current Sponsor code: EGF816
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Product Code: EGF816
Pharmaceutical Form: Capsule
Current Sponsor code: EGF816
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Secondary Objective: To characterize the safety, tolerability and pharmacokinetics of EGF816 in combination with INC280
To evaluate the preliminary anti-tumor activity of EGF816 in combination with INC280

Primary end point(s): 1-Phase Ib part: Incidence of DLTs
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
2-Baseline, every 12 weeks

Main Objective: Phase Ib part: To estimate the MTD or RP2D of EGF816 in combination with INC280
Phase II part: To estimate the preliminary anti-tumor activity of EGF816 in combination with INC280

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Phase Ib/II parts:
1-From baseline until 30 days post study treatment
2-From baseline until end of treatment
3-From start of treatment until end of treatment

Phase Ib part:
4-Baseline, every 12 weeks
5-Start of treatment, every 12 weeks
6-Start of treatment until death, average 9 months

Phase II part:
7-Baseline, every 12 weeks
8-Start of treatment, every 12 weeks
9-Start of treatment until death, average 9 months
Phase Ib/II parts:
10-First 4 cycles
Phase Ib : full PK on Days 1, 2, 15 and 16 of Cycle 1, and Days 1 and 2 of Cycle 2, & Pre-dose blood PK samples will be collected on Day 8 of Cycle 1, Day 1 of Cycle 3 and Cycle 4
Phase II: full PK on Days 1, and 2 of Cycle 1 and Cycle 2 & pre-dose PK on Day 8 of Cycle 1, Day 1 of Cycle 3 and Cycle 4

Secondary end point(s): Phase Ib/II parts:
1-Safety: AEs and SAEs
2-0Safety: hematology and chemistry values, vital signs and ECGs
3-Tolerability: Dose interruptions, reductions and dose intensity

Phase Ib part:
4- ORR, disease control rate (DCR),
5- PFS, duration of response
6- overall survival (OS)
Phase II part:
7-DCR
8- PFS duration of response
9- OS
Phase Ib/II parts:
10-Plasma concentration vs time profiles.
Plasma PK parameters of EGF816 and INC280

Secondary ID(s)

CINC280X2105C

2014-000726-37-DE

Source(s) of Monetary Support

Novartis Pharma Services AG

Ethics review

Status: Approved
Approval date: 29/01/2015
Contact: