Study of Pegilodecakin (LY3500518) With Nivolumab Compared to Nivolumab Alone Second-line Tx in Participants With Metastatic Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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To compare the efficacy of pegilodecakin in combination with nivolumab versus nivolumab alone in participants with metastatic non-small cell lung cancer as measured by objective response rate.

Detailed Description
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This is an open-label, multi-center, randomized, Phase 2 study designed to compare the efficacy and safety of pegilodecakin in combination with nivolumab versus nivolumab alone in participants with stage IV / metastatic wild type non-small cell lung cancer and tumors with low tumor expression of PD-L1 (0-49%).

Official Title
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A Randomized Phase 2 Trial of AM0010 in Combination With Nivolumab vs. Nivolumab Alone as Second-Line Therapy in Subjects With Stage IV / Metastatic Wild Type Non-Small Cell Lung Cancer and Low Tumor Expression of PD-L1

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Biological: Pegilodecakin
* Drug: Nivolumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have histologically or cytologically confirmed Wild Type NSCLC that is stage IV / metastatic or recurrent Participants must have received at least one prior systemic therapy that was not an anti-PD-1, anti-PD-L1 and/or anti-CTLA-4 treatment for the advanced stage of the disease Participants with tumor tissue low expression of PD-L1 as defined by Tumor Proportion Score (TPS) 0% - 49% Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Participants with measurable disease by spiral computed tomography (CT) or magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumor (RECIST) v.1.1 criteria Participants that have completed prior radiotherapy or radiosurgery at least 2 weeks prior to randomization Exclusion Criteria: Participants with active central nervous system (CNS) metastases or carcinomatous meningitis Participants with any serious or uncontrolled medical disorder or active infection with the hepatitis virus or the human immunodeficiency virus (HIV) Participants with Grade 1 (NCI-CTCAE v.4.03) toxicities attributed to prior anti-cancer therapy (other than alopecia and fatigue) prior to randomization Participants that have received nivolumab Participants that have received therapy with anti-tumor vaccines or other immuno-stimulatory antitumor agents Participants with a history of severe hypersensitivity reactions to monoclonal antibodies Participants that have received therapy with anti-PD-1, anti-PD-L1, anti-PD-L-2, anti-CD-137, and/or anti CTLA-4 antibodies Participants receiving any investigational agent within 28 days of first administration of trial treatment Pregnant or lactating women

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pegilodecakin+Nivolumab<br>Participants received Pegilodecakin subcutaneously at 0.8 milligrams (mg) (≤80 kilograms (kg) body weight) or 1.6 mg (>80 kg body weight) once daily (QD) in the abdomen, thigh or back of upper arm. Nivolumab administered on day 1 of each 14 or 28 day cycle over approximately 30 minutes intravenous (IV) infusion at 240 mg every 2 weeks (Q2W), or 480 mg every 4 weeks (Q4W). | Biological: Pegilodecakin<br>* Pegilodecakin plus Nivolumab<br>* Other names: AM0010;Drug: Nivolumab<br>* Nivolumab Alone<br>|
| Active Comparator: Nivolumab<br>Participants received Nivolumab on day 1 of each 14- or 28- day cycle over approximately 30 minutes intravenous (IV) infusion at 240 mg every two weeks (Q2W), or 480 mg every 4 weeks (Q4W). | Drug: Nivolumab<br>* Nivolumab Alone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] | Objective response rate is the best overall tumor response of complete response (CR) or partial response (PR) as classified by the independent central review according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. | From Date of Randomization to Progressive Disease, Death from Any cause (Up to 6 months after the last participant randomized) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is defined as the time from first day of therapy to the date of death from any cause. Participants who were alive at the end of the follow-up period or were lost to follow-up, OS was censored on the last date the participant was known to be alive. | From Date of Randomization to Death Due to Any Cause (Up to 6 months after the last participant randomized) | 
| Progression Free Survival (PFS) | PFS is defined as the time from the day of randomization to the first evidence of progression as defined by Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0) criteria or death from any cause. Progressive Disease (PD) is a 20% increase over the smallest sum of target lesions or new lesions. Participants who died without a reported prior disease progression were considered to have progressed on the day of their death. Participants who did not progress and were subsequently lost to follow-up had their data censored at the day of last tumor assessment. | From Date of Randomization to Progressive Disease or Death Due to Any Cause (Up to 6 months after the last participant randomized) | 
| Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) | Disease control rate (DCR) is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as 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 Progressive Disease or Start of New Anti-Cancer Therapy (Up to 6 Months after the last participant randomization) | 
| Duration of Response | Duration of response is defined as the time from the date measurement criteria for CR or PR (whichever is first recorded) are first met until the first date that disease is recurrent or objective progression is observed, per RECIST 1.1, or the date of death from any cause in the absence of objectively determined disease progression or recurrence. Participants known to be alive and without disease progression will be censored at the time of the last adequate tumor assessment. | From Date of Randomization to Death Due to Any Cause (Up to 6 months after the last participant randomized) |