First-line Treatment of Participants With Stage IV Squamous Non-Small Cell Lung Cancer With Necitumumab and Gemcitabine-Cisplatin (SQUIRE)

• Kaplan-Meier Estimate for Progression-free survival (PFS) [ Time Frame: Approximately 31 months ] [ Designated as safety issue: No ]
  PFS is measured from randomization to the first radiographically documented progressive disease (PD) or death. Participants alive and without disease progression or lost to follow-up will be censored to the day of their last radiographic assessment.
• Objective Response Rate(ORR) [ Time Frame: Approximately 31 months ] [ Designated as safety issue: No ]
  Proportion of participants who achieved a best overall response of complete response (CR) or partial response (PR) compared to the total number of participants. Best response is categorized using the Response Evaluation Criteria In Solid Tumors (RECIST) (ver 1.0) guidelines.
• Time to Treatment Failure (TTF) [ Time Frame: Approximately 31 months ] [ Designated as safety issue: No ]
  TTF is defined as the time from the date of randomization until the date of the first radiographic documentation of PD, death due to any cause, discontinuation of treatment for any reason, or initiation of new cancer therapy.
• Summary Listing of Participants Reporting Treatment-Emergent Adverse Events [ Time Frame: Approximately 31 months ] [ Designated as safety issue: Yes ]
  Number of participants with adverse events (AEs) collected from Day 1 [start of IMC-11F8 (necitumumab) in combination with gemcitabine-cisplatin] until 30 days after the last dose of therapy or resolution of study-related AEs. AEs will be summarized by MedRRA System Organ Class and predefined term.
• Change from baseline in Patient Reported Outcomes (PRO) using the European Quality of Life-5 Dimension (EQ-5D) at 31-months [ Time Frame: 31 months ] [ Designated as safety issue: No ]
  Change from baseline to the end of therapy visit approximately 31-months.
• Change from baseline in Patient Reported Outcomes (PRO) using the Outcomes Lung Cancer Symptom Scale (LCSS) at 31-months. [ Time Frame: 31 months ] [ Designated as safety issue: No ]
  Change from baseline to the end of therapy visit approximately 31-months.
• Minimum concentration (Cmin) of IMC-11F8 [ Time Frame: Day 1 of Cycle 1, 2, 3, 4, 5 and 6 prior to 11F8 drug infusion ] [ Designated as safety issue: No ]
• Serum Anti-IMC-11F8 (necitumumab) Antibody Assessment [ Time Frame: 31 months ] [ Designated as safety issue: Yes ]
  Number of participants who showed detectable levels of antibody at any point in the study

The research study is testing the investigational drug necitumumab (IMC-11F8) in the treatment of advanced non-small cell lung cancer. The aim of this study is to determine if necitumumab (IMC-11F8), given together with a standard chemotherapy combination consisting of cisplatin and gemcitabine will be more effective in improving patient disease than the standard chemotherapy combination alone.

Approximately 1080 patients (age ≥ 18 years) with histologically- or cytologically-confirmed, stage iv squamous-cell NSCLC, who have received no prior therapy for metastatic disease, will be randomized on a 1:1 basis to receive first-line necitumumab (IMC-11F8) plus chemotherapy consisting of gemcitabine and cisplatin in study Arm A, or gemcitabine-cisplatin chemotherapy alone in study Arm B. Baseline radiographic assessment of disease will be performed within 21 days prior to randomization (first treatment will be administered within 7 days following randomization). Patients will undergo radiographic assessment of disease status (computed tomography or magnetic resonance imaging) every 6 weeks (± 3 days), until there is radiographic documentation of progressive disease (PD). Chemotherapy will continue for a maximum of six cycles in each arm (or until there is radiographic documentation of PD, toxicity requiring cessation, protocol noncompliance or withdrawal of consent); patients in Arm A only will continue to receive necitumumab (IMC-11F8) until there is radiographic documentation of PD, toxicity requiring cessation, protocol noncompliance, or withdrawal of consent.

After the end-of-study-visit (following PD), follow-up information regarding further anticancer treatment and survival will be collected every 2 months (± 7 days). For patients who discontinue study for reasons other than PD (eg, symptomatic deterioration), information on disease progression will also be collected until PD is documented. Follow-up will continue as long as the patient is alive, or until the end of the trial.

• Biological: necitumumab

  800 mg I.V. infusion on Days 1 and 8 of every 3 week cycle.

  Continues until progressive disease, toxicity, noncompliance, or withdrawal.

  Other Names:

  • IMC-11F8
  • anti-EGFR
  • LY3012211
• Drug: gemcitabine

  1250 mg/m2 on Days 1 and 8 of every 3 week cycle.

  Continues for a maximum of six cycles.

  Other Name: Gemzar®
• Drug: cisplatin

  75 mg/m2 IV on Day 1 of every 3 week cycle.

  Continues for a maximum of six cycles.

• Experimental: necitumumab + gemcitabine + cisplatin
  necitumumab + gemcitabine + cisplatin
  Interventions:

  • Biological: necitumumab
  • Drug: gemcitabine
  • Drug: cisplatin
• Active Comparator: gemcitabine + cisplatin
  gemcitabine + cisplatin
  Interventions:

  • Drug: gemcitabine
  • Drug: cisplatin

Inclusion Criteria:

• Has histologically or cytologically confirmed squamous NSCLC
• Has Stage IV disease at the time of study entry
• Measurable or nonmeasurable disease at the time of study entry as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.0) (patients with only truly nonmeasurable disease are not eligible)
• Has resolution to Grade ≤ 1 of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy (with the exception of alopecia)
• Has adequate hepatic function
• Has adequate renal function
• Has adequate hematologic function
• If female, is surgically sterile, postmenopausal, or compliant with a highly effective contraceptive method (failure rate < 1%) during and for 6 months after the treatment period (oral hormonal contraception alone is not considered highly effective and must be used in combination with a barrier method)
• If male, the patient is surgically sterile or compliant with a highly effective contraceptive regimen during and for 6 months after the treatment period
• Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization
• Has archived tumor tissue available for analysis of EGFR and KRAS mutation status (by PCR) and EGFR gene copy number (by FISH); minimum of four slides, paraffin-embedded tissue, required

Exclusion Criteria:

• Has nonsquamous NSCLC (adenocarcinoma/large cell or other)
• Has received prior anticancer therapy with monoclonal antibodies, signal transduction inhibitors, or any therapies targeting the EGFR, vascular endothelial growth factor (VEGF), or VEGF receptor
• Has received previous chemotherapy for advanced NSCLC (patients who have received adjuvant chemotherapy are eligible if the last administration of the prior adjuvant regimen occurred at least 1 year prior to randomization)
• Has undergone major surgery or received any investigational therapy in the 4 weeks prior to randomization
• Has undergone chest irradiation within 12 weeks prior to randomization (except palliative irradiation of bone lesions, which is allowed)
• Has brain metastases that are symptomatic or require ongoing treatment with steroids or anticonvulsants. Patients who have undergone previous radiotherapy for brain metastases, who are now nonsymptomatic and no longer require treatment with steroids or anticonvulsants, are eligible
• Has superior vena cava syndrome contraindicating hydration
• Has current clinically-relevant coronary artery disease or uncontrolled congestive heart failure
• Has experienced myocardial infarction within 6 months prior to randomization
• Has an ongoing or active infection (requiring antibiotics), including active tuberculosis or known infection with the human immunodeficiency virus
• Has a history of significant neurological or psychiatric disorders, including dementia, seizures, or bipolar disorder
• Has any NCI-CTCAE Version 3.0 Grade ≥ 2 peripheral neuropathy
• Has significant third space fluid retention, requiring repeated drainage
• Has any other serious uncontrolled medical disorders or psychological conditions that would, in the opinion of the investigator, limit the patient's ability to complete the study or sign an informed consent document
• Has a known allergy / history of hypersensitivity reaction to any of the treatment components, including any ingredient used in the formulation of necitumumab (IMC-11F8), or any other contraindication to one of the administered treatments
• Is pregnant or breastfeeding
• Has a known history of drug abuse
• Has a concurrent active malignancy other than adequately-treated basal cell carcinoma of the skin or preinvasive carcinoma of the cervix. A patient with previous history of malignancy other than NSCLC is eligible, provided that he/she has been free of disease for ≥ 3 years

• Parexel
• PPD
• Medidata Solutions
• Laboratory Corporation of America
• University of Colorado, Denver
• Thermo Fisher Scientific
• ICON Clinical Research
• Pacific Biomarker Inc.
• Inostics GmbH
• Intertek