Study of Pegilodecakin (LY3500518) With Pembrolizumab Compared to Pembrolizumab Alone First-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 pembrolizumab versus pembrolizumab 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 pembrolizumab versus pembrolizumab alone in participants with stage IV / metastatic wild type non-small cell lung cancer and tumors with high expression of PD-L1 (> 50%).

Official Title
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A Randomized Phase 2 Trial of AM0010 in Combination With Pembrolizumab vs. Pembrolizumab Alone as First-Line (1L) Therapy in Patients With Stage IV / Metastatic Wild Type (WT) Non-Small Cell Lung Cancer and Tumors With High Expression of PD-L1 (> 50%)

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Biological: Pegilodecakin
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have histologically or cytologically confirmed WT NSCLC that is stage IV / metastatic or recurrent Participants with tumor tissue high expression of PD-L1 as defined by Tumor Proportion Score (TPS) ≥ 50% Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Participants with measurable disease by spiral CT or MRI per RECIST v.1.1 criteria. Participants that have completed prior radiotherapy or radiosurgery at least 2 weeks prior to randomization. Participants must be naïve to therapy for the advanced stage of the disease. Previous neoadjuvant or adjuvant therapy is allowed for participants who successfully underwent complete radical surgery and ONLY if the last treatment was administered more than 12 months prior to the start of the trial treatment 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 pembrolizumab Participants with a history of severe hypersensitivity reactions to monoclonal antibodies Pregnant or lactating women Participants receiving any investigational agent within 28 days of first administration of trial treatment Participants that have received therapy with anti-tumor vaccines or other immunostimulatory antitumor agents 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

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 + Pembrolizumab<br>Participants received pegilodecakin subcutaneously (SQ) 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. Pembrolizumab administered as an intravenous (IV) infusion at 200 mg on Day 1 of a 21-day cycle. | Biological: Pegilodecakin<br>* Pegilodecakin plus Pembrolizumab<br>* Other names: AM0010;Drug: Pembrolizumab<br>* Pembrolizumab Alone<br>|
| Active Comparator: Pembrolizumab<br>Participants received pembrolizumab as an IV infusion at 200 mg on Day 1 of a 21-day cycle. | Drug: Pembrolizumab<br>* Pembrolizumab Alone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved an Objective Response Rate (ORR) | ORR defined as the percentage of participants who achieve a CR or PR as assessed by RECIST v.1.1. The ORR is the number of participants with a complete response (CR) or partial response (PR) divided by the number of randomized participants recorded between the date of randomization and the date of objectively documented progression or the date of subsequent anti-cancer therapy, whichever comes first. Complete response (CR) is defined as disappearance of all target (and non-target) lesions, and normalization of tumor marker level. Partial response (PR) is defined as at least a 30% decrease in the sum of longest diameters of target lesions, taking as reference the baseline sum of longest diameters. | From Date of Randomization to Progressive Disease, Death from Any cause (Up to 24 Months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is defined as the time from date of randomization to death due to any cause. Participants who were alive at the end of the follow-up period or lost to follow-up were censored on the last date the participant was known to be alive. | From Date of Randomization to Death Due to Any Cause (Up to 24 Months) | 
| Progression Free Survival (PFS) | PFS is defined as the time from date of randomization to the earlier of first documentation of disease progression or death due to any cause. Progressive disease (PD) is defined by at least a 20% increase in the sum of longest diameters of target lesions, taking as reference the baseline sum of longest diameters or the presence of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression determined by scans. Participants who did not progress, who discontinued treatment for toxicity or a reason other than documented progression, or who were lost to follow up before documented progression and death or were censored at the date of last adequate tumor assessment, participants or new anticancer therapy started and not tumor progression or death were censored at the last adequate tumor assessment before the start of new anticancer therapy. | From Date of Randomization to Progressive Disease (PD) or Death Due to Any Cause (Up to 24 Months) | 
| Percentage of Participants Who Achieved a Disease Control Rate (DCR) | DCR is defined as the percentage of participants in the analysis population who have achieved a complete response (CR), partial response (PR) or stable disease (SD) response prior to disease progression. CR is defined as disappearance of all target (and non-target) lesions, and normalization of tumor marker level. PR is defined as at least a 30% decrease in the sum of longest diameters of target lesions, taking as reference the baseline sum of longest diameters. SD is defined as neither sufficient shrinkage of target lesions to qualify for partial response, nor sufficient increase to qualify for progressive disease, taking as reference the baseline sum of longest diameters. | From Date of Randomization to Objective Progressive Disease or Start of New Anti-Cancer Therapy (Up to 24 Months) | 
| Duration of Response (DOR) | DOR is defined as the time from the earliest date of qualifying response until earliest date of disease progression per RECIST v1.1 or death from any cause, whichever comes first. Duration of response was analyzed in participants who had CR or PR. Duration of response was censored on the date of the last tumor assessment on trial for participants who did not have objective tumor progression and who did not die due to any cause while on trial. For participants who discontinued participation in the trial or discontinued from tumor scan assessments before disease progression, the duration of response was censored at the date of the last tumor assessment. | From Date of Response to Death Due to Any Cause (Up to 24 Months) |