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A Phase 2 Randomized Open-label Study of Erlotinib Plus Tivantinib (ARQ 197) Versus Single Agent Chemotherapy in Previously Treated KRAS Mutation Positive Subjects With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Phase 2
18 Years
Open (Enrolling)
Metastatic Non-Small Cell Lung Cancer

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Trial Information

A Phase 2 Randomized Open-label Study of Erlotinib Plus Tivantinib (ARQ 197) Versus Single Agent Chemotherapy in Previously Treated KRAS Mutation Positive Subjects With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

This is a randomized, open-label Phase 2 study designed to compare treatment with erlotinib
plus tivantinib (ARQ 197) versus single agent chemotherapy in subjects with previously
treated KRAS mutation positive NSCLC. Eligible subjects are randomly assigned to receive
erlotinib plus tivantinib or one of three (based on Investigator's decision) single-agent
chemotherapy agents including pemetrexed, docetaxel, or gemcitabine.

Inclusion Criteria:

1. Provide signed and dated informed consent prior to study-specific screening

2. Male or female at least 18 years of age

3. Histologically or cytologically confirmed inoperable locally advanced or metastatic

4. Documented KRAS mutation positive status (per LCMC guidelines; see

5. At least one prior chemotherapy regimen for advanced NSCLC

6. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors
(RECIST) criteria, Version 1.1

7. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

8. Male or female subjects of child-producing potential must agree to use double barrier
contraception, oral contraceptives or avoidance of pregnancy measures during the
study and for 90 days after the last day of treatment

9. Females of childbearing potential must have a negative serum pregnancy test

10. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × upper limit of
normal (ULN) or ≤ 5 × ULN with metastatic liver disease

11. Total bilirubin ≤ 1.5 × ULN

12. Serum creatinine ≤ 1.5 × ULN

13. Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L

14. Platelets ≥ 100 x 10^9/L

15. Hemoglobin ≥ 10 g/dL (transfusion is allowed at least 7 days prior to randomization)

16. Subjects must agree to allow testing for c-Met status if archival and/or fresh tissue
biopsy samples are available.

Exclusion Criteria:

1. Previous receipt of erlotinib or other EGFR

2. Previous receipt of any c-MET inhibitor or other c-MET-targeted therapy, including
ARQ 197, MetMab, crizotinib

3. Prior receipt of chemotherapy agent selected for administration in this study (e.g.,
if subject was treated with gemcitabine, he is not eligible to receive gemcitabine in
this study but eligible to receive pemetrexed or docetaxel).

4. Inability or unwillingness to receive ARQ 197, erlotinib, docetaxel, gemcitabine,
and/or pemetrexed including contraindications, hypersensitivity, or prior

5. Receipt of any anti-tumor treatment for NSCLC within 3 weeks (2 weeks for
radiotherapy) prior to randomization

6. Pregnant or breastfeeding

7. Significant gastrointestinal disorder that could, in the opinion of the Investigator,
interfere with the absorption of ARQ 197 and/or erlotinib

8. Any other significant co-morbid conditions that in the opinion of the Investigator
would impair study participation or cooperation

9. Other malignancies within the last three years, with the exception of adequately
treated intraepithelial carcinoma of the cervix uteri, prostate carcinoma with a PSA
value < 0.2 ng/mL or basal or squamous cell carcinoma of the skin

10. Known human immunodeficiency virus (HIV), or active hepatitis B virus (HBV) or
hepatitis C virus (HCV) infection

11. Major surgical procedure within 4 weeks prior to randomization

12. History of cardiac disease: Congestive heart failure defined as Class II to IV per
New York Heart Association classification; Active coronary artery disease; Previously
diagnosed bradycardia or other cardiac arrhythmia defined as ≥ Grade 2 according to
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events
(CTCAE), version 4.0, or uncontrolled hypertension; Myocardial infarction that
occurred within 6 months prior to study entry (myocardial infarction that occurred >
6 months prior to study entry is permitted)

13. Clinically unstable central nervous system metastasis (to be enrolled in the study,
subjects must have confirmation of stable disease by MRI or CT scan within 4 weeks of
randomization and have CNS metastases well controlled by steroids, anti-epileptics or
other symptom-relieving medications)

14. Known EGFR-mutation positive status

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The primary objective of this study is to evaluate median progression-free survival (PFS) among subjects with KRAS mutation positive NSCLC (ITT population) treated with erlotinib plus ARQ 197 compared to single agent chemotherapy.

Outcome Time Frame:

Date of randomization until disease progression per RECIST (Version 1.1) or death from any cause, whichever came first, assessed up to 24 months.

Safety Issue:



United States: Food and Drug Administration

Study ID:

ARQ 197-218



Start Date:

July 2011

Completion Date:

December 2013

Related Keywords:

  • Metastatic Non-Small Cell Lung Cancer
  • KRAS mutation
  • metastatic NSCLC
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



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