A Phase 2, Study of Ficlatuzumab Plus Erlotinib vs. Placebo Plus Erlotinib in Subjects With Previously Untreated Metastatic, EGFR-mutated NSCLC and BDX004 Positive Label

Phase 2 multicenter, controlled, randomized, double-blind study to evaluate the efficacy and safety of ficlatuzumab versus placebo when administered with erlotinib in subjects with previously untreated metastatic EGFR-mutated NSCLC and BDX004 Positive Label.

This is a Phase 2 multicenter, controlled, randomized, double-blind study to evaluate the efficacy and safety of ficlatuzumab versus placebo when administered with erlotinib in subjects with previously untreated metastatic EGFR-mutated NSCLC and BDX004 Positive Label.

Prior to screening, subjects will have tested positive for a sensitizing EGFR mutation to determine eligibility for treatment with erlotinib. During screening, subject serum samples will be tested using the investigational companion diagnostic (BDX004) test. Only those subjects who have a BDX004 Positive Label will be enrolled. Subject randomization will be stratified by EGFR mutation type and smoking status (ever versus never smokers). Subjects will be designated as never smokers if they have smoked less than 100 cigarettes in their lifetime. Radiographic tumor assessment, to include CT or MRI of chest and abdomen, will be performed every 4 weeks for the first 8 cycles, and every 8 weeks thereafter, using the same imaging modality per subject. Safety assessments will be performed on an ongoing basis.

Eligibility Criteria:
Inclusion Criteria

* Histologically and/or cytologically confirmed primary diagnosis of Stage IV NSCLC (according to American Joint Committee on Cancer \[AJCC\] 7th edition lung cancer staging criteria).
* Measurable disease according to RECIST v.1.1.
* An EGFR exon 19 deletion and/or an exon 21 (L858R) substitution mutation.
* BDX004 Positive Label.
* Have received no prior systemic chemotherapy, immunotherapy, targeted therapy, or biologic therapy for metastatic NSCLC. Subjects may have previously been treated with postoperative adjuvant chemotherapy for early stage lung cancer or chemo radiotherapy for locally advanced disease provided this was completed at least 6 months prior to enrollment. No prior EGFR TKI therapy is allowed for any stage of NSCLC.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Exclusion Criteria
* History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational agent or erlotinib.
* History of known brain metastases.
* Prior treatment with any other investigational drug or biologic agent within 5 half lives prior to randomization, or any investigational device within 2 weeks prior to randomization.
* Any unresolved toxicity from previous radiation therapy.
* Significant cardiovascular disease, including:

  * Echocardiogram (ECHO) or multiple gated acquisition (MUGA) showing left ventricular ejection fraction of less than 55%.
  * Cardiac failure New York Heart Association class III or IV.
  * Myocardial infarction, severe or unstable angina within 6 months prior to randomization.
  * History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation).
  * Significant thrombotic or embolic events within 3 months prior to randomization (significant thrombotic or embolic events include but are not limited to stroke or transient ischemic attack).
  * Any uncontrolled or severe cardiovascular disease.
* History of prior malignancy within 3 years prior to randomization (except for adequately treated non-melanoma skin cancer, carcinoma in situ of the breast or cervix, superficial bladder cancer, or early stage prostate cancer, without evidence of recurrence).
* Radiographic evidence of interstitial lung disease.