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

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

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.

Inclusion Criteria

1. Male or female at least 20 years of age with life expectancy ≥ 3 months

2. 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

3. Evaluable disease according to RECIST, Version 1.1

4. 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

5. ECOG performance status of 0 or 1

6. 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.

7. Voluntary written informed consent form before performance of any study-specific procedures or tests

Exclusion Criteria

1. Prior therapy with an EGFR inhibitor and/or tivantinib
2. Any systemic anti-tumor treatment for NSCLC or investigational agents within 4 weeks prior to randomization
3. 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
4. Major surgical procedure within 4 weeks prior to randomization
5. History of cardiac disease
6. Known symptomatic brain metastases
7. Need to breastfeed a child during or within 12 weeks of completing the study
8. Significant gastrointestinal disorder that could interfere with absorption of tivantinib and/or erlotinib
9. History of malignancy other than NSCLC
10. Known infection with HIV, active HBV or HCV
11. Clinically significant interstitial lung diseases detected by CT scan or prior history of such diseases
12. Psychiatric disease that could affect the informed consent process
13. Subjects who wish to have a child and who would not agree to use one or more contraceptive measures that are highly effective
14. Positive serum or urine pregnancy test in female subjects of childbearing potential
15. Any other significant co-morbid condition that, in opinion of the investigator/sub-investigator, would impair study participation or cooperation