A Phase 3, Randomized, Double-Blinded, Placebo-Controlled Study of ARQ 197 Plus Erlotinib Versus Placebo Plus Erlotinib

Study Overview
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Brief Summary
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The primary objective of this study is to determine if the combination regimen of ARQ 197 with erlotinib will improve overall survival (OS) compared to erlotinib monotherapy in subjects with locally advanced or metastatic non-squamous NSCLC with wild-type EGFR who have received 1 or 2 prior systemic anti-cancer therapies in the Intent-to-Treat (ITT) population.

Official Title
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A Phase 3, Randomized, Double-Blinded, Placebo-Controlled Study of ARQ 197 Plus Erlotinib Versus Placebo Plus Erlotinib in Previously Treated Subjects With Locally Advanced or Metastatic, Non-Squamous, Non-Small-Cell Lung Cancer With Wild-type Epidermal Growth Factor Receptor

Conditions
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Non-small-cell Lung Cancer

Intervention / Treatment
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* Drug: ARQ 197 and Erlotinib
* Drug: Placebo and Erlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Male or female at least 20 years of age with life expectancy ≥ 3 months Histologically or cytologically confirmed surgically unresectable locally advanced or metastatic (stage IIIB/IV) non-squamous NSCLC with wild-type (excluding major activating mutation (exon 19 deletion and/or exon 21 L858R mutation)) EGFR gene status confirmed by a highly sensitive PCR assay Evaluable disease according to RECIST, Version 1.1 Received one or two prior lines of systemic anti-cancer therapy for advanced or metastatic disease, one of which must be a platinum-based therapy ECOG performance status of 0 or 1 Demonstrate adequate bone marrow, liver, and renal functions, defined as: • ALT and AST ≤ 2.5 × upper limit of normal (ULN), total bilirubin ≤ 1.5 × ULN, ANC ≥1.5 × 10^9/L, platelet count ≥100 × 10^9/L, hemoglobin ≥9.0 g/dL, and serum creatinine ≤1.5 mg/dL. Voluntary written informed consent form before performance of any study-specific procedures or tests Exclusion Criteria Prior therapy with an EGFR inhibitor and/or tivantinib Any systemic anti-tumor treatment for NSCLC or investigational agents within 4 weeks prior to randomization Palliative radiotherapy within 2 weeks, or radiotherapy for curative intent of target lesions within 8 weeks for chest and within 4 weeks for other areas prior to randomization Major surgical procedure within 4 weeks prior to randomization History of cardiac disease Known symptomatic brain metastases Need to breastfeed a child during or within 12 weeks of completing the study Significant gastrointestinal disorder that could interfere with absorption of tivantinib and/or erlotinib History of malignancy other than NSCLC Known infection with HIV, active HBV or HCV Clinically significant interstitial lung diseases detected by CT scan or prior history of such diseases Psychiatric disease that could affect the informed consent process Subjects who wish to have a child and who would not agree to use one or more contraceptive measures that are highly effective Positive serum or urine pregnancy test in female subjects of childbearing potential Any other significant co-morbid condition that, in opinion of the investigator/sub-investigator, would impair study participation or cooperation

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARQ 197<br>ARQ 197 and Erlotinib | Drug: ARQ 197 and Erlotinib<br>* Oral twice daily administration of ARQ197 and oral once daily administration of erlotinib<br>|
| Placebo Comparator: Placebo<br>Placebo and Erlotinib | Drug: Placebo and Erlotinib<br>* Oral twice daily administration of placebo and oral once daily administration of erlotinib<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival |  |  | 
| Objective response rate | Each assessment will be determined based on RECIST criteria version 1.1 by investigator |  | 
| Number of patients with adverse events |  |  |