A Study of Nab-Paclitaxel and Carboplatin Plus Necitumumab (LY3012211) in Participants With Stage IV Squamous NSCLC

Study Overview
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Brief Summary
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The purpose of the study is to determine if nab-paclitaxel and carboplatin chemotherapy plus necitumumab is effective and safe in participants with stage IV squamous non-small cell lung cancer.

Official Title
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A Single-Arm, Multicenter, Open-Label, Phase 2 Study of Nab®-Paclitaxel (Abraxane®) and Carboplatin Chemotherapy Plus Necitumumab (LY3012211) in the First-Line Treatment of Patients With Stage IV Squamous Non-Small Cell Lung Cancer (NSCLC)

Conditions
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Carcinoma, Non-Small Cell Lung Cancer (NSCLC)

Intervention / Treatment
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* Drug: Necitumumab
* Drug: Nab-Paclitaxel
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have histologically or cytologically confirmed squamous NSCLC. Have stage IV disease at the time of study entry (American Joint Committee on Cancer [AJCC] Staging Manual, 7th edition). Have measurable disease at the time of study enrollment as defined by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1). Have tumor tissue available for biomarker analysis. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Have adequate organ functions. Exclusion Criteria: Are currently enrolled in another clinical trial. Have received prior anticancer therapy with monoclonal antibodies, signal transduction inhibitors, or any therapies targeting the epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), or VEGF receptor. Have received previous chemotherapy for advanced NSCLC. Participants who have received adjuvant or neoadjuvant chemotherapy are eligible if the last administration of the prior regimens occurred at least 1 year prior to study entry. Have undergone major surgery or received any investigational therapy in the 4 weeks prior to study entry. Have undergone systemic radiotherapy within 4 weeks prior to study entry, or focal radiotherapy within 2 weeks prior to study entry. Have symptomatic central nervous system (CNS) malignancy or metastasis (screening not required). Have a history of arterial or venous embolism within 6 months prior to study entry. Have clinical evidence of concomitant infectious conditions. Have a known allergy / history of hypersensitivity reaction to any of the treatment components, including any ingredient used in the formulation of necitumumab, or any other contraindication to one of the administered treatments. Are pregnant or breastfeeding. Have a known history of drug abuse. Have a concurrent active malignancy. Participants with a history of malignancy are eligible provided the participant has been disease-free for ≥3 years, with the following exception: Participants with adequately treated basal or squamous cell carcinoma of the skin, preinvasive carcinoma of the cervix, or any cancer that in the judgment of the investigator and Lilly clinical research physician/designee may not affect the interpretation of results (for example, prostate, bladder) are eligible. Have discontinued investigational product or non approved use of a drug or device from a clinical trial within 30 days before the first day of study treatment.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Necitumumab + Nab-Paclitaxel + Carboplatin<br>Induction: Necitumumab administered intravenously (IV) at 800 milligram (mg) on day 1 and 8 of each cycle (3 week cycles); nab-paclitaxel administered IV at 100 milligram per square meter (mg/m²) on day 1, 8 and 15 of each cycle; carboplatin administered IV at a concentration of AUC (area under curve) 6 milligram per milliliter over time (mg*min/mL) on day 1 of each cycle, for a maximum of 4 cycles. Maintenance: Necitumumab administered IV at 800 mg on day 1 and 8 of each cycle; nab-paclitaxel administered IV at 100mg/m² on day 1 and 8 of each cycle (3 week cycles). Participants may continue to receive treatment until discontinuation criteria are met. | Drug: Necitumumab<br>* Administered IV<br>* Other names: IMC-11F8;Drug: Nab-Paclitaxel<br>* Administered IV<br>* Other names: Abraxane;Drug: Carboplatin<br>* Administered IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response or Partial Response (Objective Tumor Response Rate [ORR]) | ORR was the percentage of participants achieving a best overall response of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of nontarget lesions, and no appearance of new lesions. Progressive disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. | From Date of Randomization to Objective Disease Progression (Up to 18 Months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS defined as time from date of randomization until first radiographic documentation of measured PD defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. PD was at least 20% increase in sum of diameters of target lesions with reference being smallest sum on study and an absolute increase of at least 5 mm,or unequivocal progression of non-target lesions,or 1 or more new lesions.If participant does not have complete baseline disease assessment,PFS time censored at date of randomization,regardless of whether or not objectively determined disease progression or death observed for participant.If participant was not known to have died or have objective progression as of data inclusion cutoff date for analysis,the PFS time censored at last adequate tumor assessment date.The use of new anticancer therapy prior to occurrence of PD resulted in censoring at the date of last radiographic assessment prior to initiation of new therapy. | From Date of Randomization to Measured Progressive Disease or Death Due to Any Cause (Up to 18 Months) | 
| Overall Survival (OS) | OS defined as the time from the date of randomization to the date of death due to any cause. Participants who are alive at the time of study completion or are lost to follow-up will be censored at the time they were last known to be alive. | From Date of Randomization until Death Due to Any Cause (Up to 18 Months) | 
| Percentage of Participants Who Achieve Best Overall Disease Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) (Disease Control Rate [DCR]) | Disease Control Rate (DCR) was the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1 criteria. CR defined as the disappearance of all target and nontarget lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. | From Date of Randomization to Objective Disease Progression or Start of New Anticancer Therapy (Up to 18 Months) | 
| Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab, Nab-Paclitaxel, and Carboplatin | The Cmin is the minimum observed serum/plasma concentration of Necitumumab, Nab-Paclitaxel, and Carboplatin. | Cycle 3 and cycle 4: predose | 
| PK: Maximum Concentration (Cmax) of Necitumumab, Nab-Paclitaxel, and Carboplatin | The Cmax is the maximum observed serum/plasma concentration of Necitumumab, Nab-Paclitaxel, and Carboplatin. | Cycle 1, 3 and 4: predose and <15minutes (min) post end-of-infusion | 
| Immunogenicity: Number of Participants Developing Anti-drug Antibodies to Necitumumab | A participant was considered to have an anti-drug antibody response if anti-drug antibodies (ADA) were detected at any time point. | Predose Cycle 1 Through Short Term Follow Up (Up To 18 Months) |