Pembrolizumab/Vibostolimab Coformulation (MK-7684A) or Pembrolizumab/Vibostolimab Coformulation Plus Docetaxel Versus Docetaxel for Metastatic Non Small Cell Lung Cancer (NSCLC) With Progressive Disease After Platinum Doublet Chemotherapy and Immunotherapy (MK-7684A-002, KEYVIBE-002)

Study Overview
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Brief Summary
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The main purpose of this study is to compare pembrolizumab/vibostolimab coformulation (MK-7684A) plus docetaxel or pembrolizumab/vibostolimab coformulation to normal saline placebo plus docetaxel. Participants with metastatic non-small cell lung cancer (NSCLC) and progressive disease (PD) after platinum doublet chemotherapy and treatment with one prior anti- programmed cell death 1 (PD-1)/ programmed cell death ligand 1(PD-L1) monoclonal antibody (mAb). MK-7684A is a coformulation product of pembrolizumab/vibostolimab. The dual primary hypotheses of the study are pembrolizumab/vibostolimab coformulation plus docetaxel and pembrolizumab/vibostolimab coformulation is superior to normal saline placebo plus docetaxel with respect to progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR).

Detailed Description
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Participants may receive additional 17 cycles of pembrolizumab/vibostolimab (each cycle length = 21 days) for an additional 1 year of treatment as second course phase at investigator's discretion.

Official Title
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A Phase 2, Multicenter, Randomized Study to Compare the Efficacy and Safety of MK-7684A or MK-7684A Plus Docetaxel Versus Docetaxel Monotherapy in the Treatment of Participants With Metastatic Non-small Cell Lung Cancer With Progressive Disease After Treatment With a Platinum Doublet Chemotherapy and Immunotherapy

Conditions
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Metastatic Non Small Cell Lung Cancer

Intervention / Treatment
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* Biological: Pembrolizumab/Vibostolimab coformuation
* Drug: Docetaxel
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a histologically or cytologically confirmed diagnosis of metastatic non-small cell lung cancer (NSCLC) Has confirmation that epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or reactive oxygen species (ROS) 1 directed therapy is not indicated as primary therapy Has progressive disease (PD) on treatment with one prior anti-programmed cell death 1 (PD-1)/ programmed cell death ligand 1 (PD-L1) monoclonal antibody (mAb) administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies Retreatment with the same anti-PD-L1/PD-L1 mAb is acceptable in the overall course of treatment Has PD as determined by the investigator after platinum doublet chemotherapy for metastatic disease Has measurable disease defined as at least 1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI), based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Has provided tumor tissue for PD-L1 biomarker analysis from an archival sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated Has a life expectancy of at least 3 months Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 assessed within 7 days prior to randomization Male participants randomized to docetaxel are eligible to participant if they agree to refrain from donating sperm, and either 1) be abstinent from heterosexual intercourse; or 2) must agree to follow contraceptive guidance as per study protocol unless confirmed to be azoospermic during the intervention period and for at least 180 days after the last dose of docetaxel Female participants must be not pregnant, not breastfeeding, and not be a woman of child-bearing potential (WOCBP). A WOCBP is eligible is she agrees to either use contraception, or be abstinent from heterosexual intercourse during the intervention period and for ≥120 days after the last dose of study intervention. If a WOCBP is randomized to docetaxel, she agrees not to donate eggs and either uses contraception or be abstinent from heterosexual intercourse during the treatment period and for ≥180 days after the last dose of docetaxel Has adequate organ function Exclusion Criteria: Has known active or untreated central nervous system (CNS) metastases and/or carcinomatous meningitis Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for at least 3 years since initiation of that therapy Has received docetaxel as monotherapy or in combination with other therapies Has received previous treatment with another agent targeting the T-cell immunoreceptor with immunoglobulin [Ig] and immunoreceptor tyrosine-based inhibitory motif [ITIM] domains (TIGIT) pathway Has received radiotherapy within 2 weeks of start of study intervention. One week washout is permitted for palliative radiation to non-CNS disease Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention Has severe hypersensitivity (≥Grade 3) to docetaxel or pembrolizumab/vibostolimab coformulation and/or any of its excipients Has an active autoimmune disease that has required systemic treatment in past 2 years Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of study intervention Has interstitial lung disease, or history of pneumonitis requiring steroids for treatment Has known history of active human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C Has had an allogenic tissue/solid organ transplant Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Pembrolizumab/Vibostolimab coformulation + Docetaxel<br>Participants receive pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years plus docetaxel 75 mg/m^2 IV infusion Q3W until discontinuation due to progressive disease or unacceptable toxicity. | Biological: Pembrolizumab/Vibostolimab coformuation<br>* Pembrolizumab 200 mg + vibostolimab 200 mg/20 mL vial IV infusion Q3W up to approximately 2 years.<br>* Other names: MK-7684A;Drug: Docetaxel<br>* Docetaxel 75 mg^m2 IV infusion Q3W until discontinuation due to progressive disease or unacceptable toxicity. Docetaxel will serve as part of an experimental treatment in Arm 1, and as an active comparator in Arm 3.<br>* Other names: Taxotere;|
| Experimental: Arm 2: Pembrolizumab/Vibostolimab coformulation<br>Participants receive pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via IV infusion Q3W for up to 35 cycles up to approximately 2 years. | Biological: Pembrolizumab/Vibostolimab coformuation<br>* Pembrolizumab 200 mg + vibostolimab 200 mg/20 mL vial IV infusion Q3W up to approximately 2 years.<br>* Other names: MK-7684A;|
| Active Comparator: Arm 3: Placebo + Docetaxel<br>Participants receive normal saline IV infusion, Q3W for up to 35 cycles up to approximately 2 years plus Docetaxel 75 mg/m^2 IV infusion Q3W until discontinuation due to progressive disease or unacceptable toxicity. | Drug: Docetaxel<br>* Docetaxel 75 mg^m2 IV infusion Q3W until discontinuation due to progressive disease or unacceptable toxicity. Docetaxel will serve as part of an experimental treatment in Arm 1, and as an active comparator in Arm 3.<br>* Other names: Taxotere;Drug: Placebo<br>* Normal saline IV infusion Q3W up to approximately 2 years<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) Assessment | PFS is defined as the time from randomization to the first documented disease progression (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented | Up to approximately 27 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response (OR) per RECIST 1.1 by BICR Assessment | OR is defined as a confirmed complete response (CR: Disappearance of all target lesions) or a partial response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience a CR or PR as assessed by BICR based on RECIST 1.1 will be presented. | Up to approximately 27 months | 
| Overall Survival (OS) | OS is defined as the time from randomization to the date of death due to any cause. | Up to approximately 77 months | 
| Duration of Response (DOR) per RECIST 1.1 by BICR Assessment | For participants who demonstrate a confirmed CR (Disappearance of all target lesions) or confirmed PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. The DOR as assessed by BICR will be presented. | Up to approximately 77 months | 
| Number of Participants Who Experienced an Adverse Event (AE) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Number of participants who experience an AE will be reported. | Up to approximately 77 months | 
| Number of Participants Who Discontinued Study Treatment Due to an AE | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Number of participants who discontinue study treatment due to an AE will be reported. | Up to approximately 37 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Programmed Cell Death Receptor 1 (PD-1), Programmed Cell Death Receptor Ligand 1 (PD-L1), Programmed Cell Death Receptor Ligand 2 (PD-L2), PD-1, PDL1, PD-L1, PD-L2