Phase I/II study to evaluate safety and activity of oral administration of S 49076 in combination with gefitinib in adult patients with EGFR mutated advanced non-small cell lung cancer who have progressed while on treatment with EGFR tyrosine kinase inhibitor (TKI) therapy.

Phase I/II study of oral administration of S 49076 given in combination with gefitinib in patients with EGFR mutated advanced non-small-cell lung cancer who have progressed after treatment with EGFR tyrosine kinase inhibitor.

Status

Active, not recruiting

Phases

Phase 1Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2015-002646-31-ES

Enrollment

171

Registered

2015-10-05

Start date

2015-12-10

Completion date

Unknown

Last updated

2018-12-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Locally advanced or metastatic non-small-cell lung cancer MedDRA version: 18.0 Level: LLT Classification code 10025054 Term: Lung cancer non-small cell stage IIIB System Organ Class: 100000004864 MedDRA version: 18.0 Level: LLT Classification code 10025055 Term: Lung cancer non-small cell stage IV System Organ Class: 100000004864

Interventions

Product Code: S49076 Pharmaceutical Form: Tablet INN or Proposed INN: NA CAS Number: NA Current Sponsor code: S49076 Other descriptive name: S49076 Concentration unit: mg milligram(s) Concentration ty

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: -Male or female patient aged ? 18 years old or legal age of the majority in the country. -Histologically or cytologically confirmed stage IIIB/IV NSCLC ( locally advanced or metastatic, non-eligible for radical chemoradiotherapy or surgery with curative intention). -Progression will have occurred on single agent EGFR TKI treatment (erlotinib, gefitinib, icotinib, afatinib) in the 1st line setting or in the 2nd line (after a first line of chemotherapy). -Patients must meet definition of acquired resistance based on the modified Jackman criteria. -Patients must have measurable tumour disease according to RECIST v1.1. (with at least one measurable lesion). -Estimated life expectancy > 12 weeks. -Eastern Cooperative Oncology Group (ECOG) performance status ? 1 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 114 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 57

Exclusion criteria

Exclusion criteria: -Foreseeable poor compliance to the study procedures. -Legally incapacitated person under guardianship or trusteeship. -Pregnant or breast-feeding women. -Unable to undergo CT scans or MRI. -Patients who have received more than 1 line of chemotherapy and more than 1 line of erlotinib, gefitinib, icotinib or afatinib. -Blood transfusion within 2 weeks prior to the inclusion. -Major surgery within 4 weeks prior to the inclusion. -Prior radiotherapy within 4 weeks prior to the inclusion.

Design outcomes

Primary

Measure	Time frame
Main Objective: Phase I: -Determine the safety profile and tolerability of S 49076 given in combination with a fixed dose of gefitinib by assessment of DLT (assessed during cycle 1) and the adverse event profile (assessed at each study visit). -Establish the RP2D of S 49076 given in combination with a fixed dose of gefitinib. Phase II: -Evaluate the objective response rate (ORR) according to RECIST v1.1, in 3 subgroups of patients with locally advanced or metastatic NSCLC and treated with S 49076 and gefitinib defined according to the mechanism of acquired resistance to EGFR tyrosine kinase inhibitor (TKI): ? Subgroup 1: Moderate to high level of MET amplification and/or overexpression ? Subgroup 2: Moderate level of AXL overexpression ? Subgroup 3: High level of AXL overexpression. An interim analysis will be performed in each subgroup to stop the recruitment early for futility if it is clear that the association S 49076 and gefitinib is unlikely to show the expected benefit.;Secondary Objective: Phase I:-Evaluate the PK profile of S 49076 and gefitinib in combination. -Evaluate the response to S 49076 and gefitinib in 3 subgroups of patients with MET and/or AXL dysregulation using archived tumour or newly performed biopsy. -Measure tumour response to S 49076 in combination with gefitinib by using RECIST v1.1. Phase II:-Evaluate the survival rate at 6 months, the progression-free survival, the response duration, the Clinical Benefit Rate in the 3 subgroups of patients. Clinical benefit rate is defined as the proportion of patients who have confirmed Complete Response or Partial Response as best response, or who experience Stable Disease lasting at least 6 months in the 3 subgroups of patients. -Characterize the safety and tolerability of the combination in assessing incidence of adverse events according to CTCAE V4.0. -Collect additional information on the PK profile of S 49076 in combination with gefitinib. -Evaluate the biomarkers potentially predictive of respon	—

Measure

Time frame

Main Objective: Phase I: -Determine the safety profile and tolerability of S 49076 given in combination with a fixed dose of gefitinib by assessment of DLT (assessed during cycle 1) and the adverse event profile (assessed at each study visit). -Establish the RP2D of S 49076 given in combination with a fixed dose of gefitinib. Phase II: -Evaluate the objective response rate (ORR) according to RECIST v1.1, in 3 subgroups of patients with locally advanced or metastatic NSCLC and treated with S 49076 and gefitinib defined according to the mechanism of acquired resistance to EGFR tyrosine kinase inhibitor (TKI): ? Subgroup 1: Moderate to high level of MET amplification and/or overexpression ? Subgroup 2: Moderate level of AXL overexpression ? Subgroup 3: High level of AXL overexpression. An interim analysis will be performed in each subgroup to stop the recruitment early for futility if it is clear that the association S 49076 and gefitinib is unlikely to show the expected benefit.;Secondary Objective: Phase I:-Evaluate the PK profile of S 49076 and gefitinib in combination. -Evaluate the response to S 49076 and gefitinib in 3 subgroups of patients with MET and/or AXL dysregulation using archived tumour or newly performed biopsy. -Measure tumour response to S 49076 in combination with gefitinib by using RECIST v1.1. Phase II:-Evaluate the survival rate at 6 months, the progression-free survival, the response duration, the Clinical Benefit Rate in the 3 subgroups of patients. Clinical benefit rate is defined as the proportion of patients who have confirmed Complete Response or Partial Response as best response, or who experience Stable Disease lasting at least 6 months in the 3 subgroups of patients. -Characterize the safety and tolerability of the combination in assessing incidence of adverse events according to CTCAE V4.0. -Collect additional information on the PK profile of S 49076 in combination with gefitinib. -Evaluate the biomarkers potentially predictive of respon

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Secondary

Measure	Time frame
Secondary end point(s): Phase I: 1-PK parameters of S 49076 and gefitinib in combination. 2-Biomarkers predictive of response using archived tumours or newly performed biopsy. 3-Tumour response of S 49076 in combination with gefitinib by using RECIST v1.1. Phase II: I.Activity: 1-Survival rate. 2-Progression Free Survival (PFS). 3-Clinical Benefit Rate (CBR). 4-Response duration. II.Safety tolerance profile. III.PK parameters of S 49076 in combination with gefitinib. IV.Biomarkers predictive of response.;Timepoint(s) of evaluation of this end point: Phase I: 1-:D1, D2 and D15 of cycle 1 and D1 of cycle 2. 2-:D1 of each cycle. 3-:Screening visit, D1 Cycle 3 and withdrawal visit. Phase II: I.1-:-at 6 months. 2-:will be calculated from the date of first drug intake until the date of progression or death due to any cause, whichever occurs first. 3-:will be calculated as the proportion of patients with a confirmed CR or PR or a SD with duration of at least 6 months according to RECIST v1.1. 4-:will be calculated among patients with confirmed response from the time that measurement criteria are first met for response until the date of progression or death due to any cause. II.: All visits III.: D1, D2 and D15 of cycle 1, and D1 of cycle 2. IV.: D1 of each cycle.	—

Measure

Time frame

Secondary end point(s): Phase I: 1-PK parameters of S 49076 and gefitinib in combination. 2-Biomarkers predictive of response using archived tumours or newly performed biopsy. 3-Tumour response of S 49076 in combination with gefitinib by using RECIST v1.1. Phase II: I.Activity: 1-Survival rate. 2-Progression Free Survival (PFS). 3-Clinical Benefit Rate (CBR). 4-Response duration. II.Safety tolerance profile. III.PK parameters of S 49076 in combination with gefitinib. IV.Biomarkers predictive of response.;Timepoint(s) of evaluation of this end point: Phase I: 1-:D1, D2 and D15 of cycle 1 and D1 of cycle 2. 2-:D1 of each cycle. 3-:Screening visit, D1 Cycle 3 and withdrawal visit. Phase II: I.1-:-at 6 months. 2-:will be calculated from the date of first drug intake until the date of progression or death due to any cause, whichever occurs first. 3-:will be calculated as the proportion of patients with a confirmed CR or PR or a SD with duration of at least 6 months according to RECIST v1.1. 4-:will be calculated among patients with confirmed response from the time that measurement criteria are first met for response until the date of progression or death due to any cause. II.: All visits III.: D1, D2 and D15 of cycle 1, and D1 of cycle 2. IV.: D1 of each cycle.

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Countries

Australia, China, Germany, Hong Kong, Hungary, Italy, Korea, Republic of, Malaysia, Philippines, Poland, Singapore, Spain, Taiwan, Thailand, United Kingdom

Contacts

Public ContactDpto. Investigación y Desarrollo

Laboratios Servier S.L.

itziar.fernandezgonzalez@servier.com+34917489014

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026