PEMBROLIZUMAB for Non-small cell lung cancer (NSCLC) | Squamous non-small cell lung cancer | Non-squamous non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- Has pathologically (histologically or cytologically) confirmed diagnosis of squamous or nonsquamous non-small cell lung cancer (NSCLC)\n- Has adequate organ function\n- Has Stage IV (T any, N any, M1a, M1b, or M1c - American Joint Committee on Cancer 8th Edition) squamous or nonsquamous NSCLC\n- Has confirmation that epidermal growth factor receptor (EGFR), Anaplastic lymphoma kinase (ALK), or Receptor Tyrosine Kinase 1 (ROS1)-directed therapy is not indicated in nonsquamous NSCLC as well as mixed nonsquamous/squamous NSCLC. Participants with purely squamous NSCLC do not require testing\n- Has not received prior systemic treatment for their metastatic NSCLC. Participants who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the development of metastatic disease\n- Has an Eastern Cooperative Oncology Group (ECOG) performance score (PS) of 0 or 1\n- Male participants are eligible to participate if they agree to use contraception as per protocol unless confirmed to be azoospermic\n- A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP) or is a WOCBP who agrees of using a contraceptive method per protocol\n- Has measurable disease per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by the local site investigator/radiology\n- Submit an archival tumor tissue sample or newly obtained core or incisional biopsy of a tumor lesion not previously irradiated for PD-L1 status determination prior to randomization"}

Exclusion criteria

• {"criterion_text":"- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years\n- Before the first dose of study intervention: a) Has received prior systemic cytotoxic chemotherapy for metastatic NSCLC b) Has received antineoplastic biological therapy for metastatic NSCLC c) Has had major surgery (<3 weeks prior to first dose) d) Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti-programmed cell death ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor\n- Received radiation therapy to the lung that is >30 Gray within 6 months of the first dose of study intervention\n- Is expected to require any other form of antineoplastic therapy while on study\n- For participants with nonsquamous histology: Is unable to interrupt aspirin or other Non-steroidal anti-inflammatory drugs (NSAIDs), other than an aspirin dose ≤1.3 g/day, for a 5-day period\n- For participants with nonsquamous histology: Is unable or unwilling to take folic acid or vitamin B12 supplementation\n- Has received prior radiotherapy within 2 weeks of start of study intervention or have had a history of radiation pneumonitis. Participants must have recovered from all radiation-related toxicities and not require corticosteroids. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease\n- Has received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention\n- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention\n- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention\n- Has had an allogenic tissue/solid organ transplant\n- Has known central nervous system (i.e., brain and/or spinal cord) metastases and/or carcinomatous meningitis. Participants with treated brain metastases may participate only if they satisfy all of the following: a) Have no evidence of new or enlarging brain metastases confirmed by post-treatment repeat brain imaging performed at least 4 weeks after pretreatment brain imaging, and b) Are neurologically stable without the need for steroids for at least 14 days before first dose of trial treatment as per local site assessment\n- Has severe hypersensitivity to study intervention and/or any of its excipients\n- Has an active autoimmune disease that has required systemic treatment in past 2 years\n- Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease\n- Has an active infection requiring systemic therapy\n- Has a known history of human immunodeficiency virus (HIV) infection and/or Hepatitis B infection or known active Hepatitis C infection\n- Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study\n- Has symptomatic ascites or pleural effusion. A participant who is clinically stable after treatment for these conditions is eligible"}

Primary endpoints

• {"endpoint_text":"- Area Under The Curve From 0-3 Weeks (AUC 0-3wks) of Pembrolizumab at Cycle 1","definition_or_measurement_approach":"Compare AUC between pembrolizumab subcutaneous (SC) vs intravenous (IV); measured by pharmacokinetic sampling (AUC 0–3 weeks) at Cycle 1 and PK analysis."}
• {"endpoint_text":"- Cycle 6 Model-Based Minimal Concentration (Ctrough) of Pembrolizumab","definition_or_measurement_approach":"Compare model-based Ctrough of pembrolizumab at Cycle 6 between SC and IV administration using PK sampling and model-based PK analysis."}

Secondary endpoints

• {"endpoint_text":"- Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)","definition_or_measurement_approach":"Measured per RECIST 1.1; assessed by blinded independent central review (BICR)."}
• {"endpoint_text":"- Observed Ctrough of Pembrolizumab at the End of Cycle 1","definition_or_measurement_approach":"Observed trough concentration measured at end of Cycle 1 by PK sampling."}
• {"endpoint_text":"- Maximum Concentration (Cmax) of Pembrolizumab at Cycle 1","definition_or_measurement_approach":"Measured Cmax at Cycle 1 by PK sampling."}
• {"endpoint_text":"- AUC 0-3wks of Pembrolizumab at Cycle 6","definition_or_measurement_approach":"AUC 0–3 weeks at Cycle 6 measured by PK sampling and analysis."}
• {"endpoint_text":"- Cmax of Pembrolizumab at Cycle 6","definition_or_measurement_approach":"Measured Cmax at Cycle 6 by PK sampling."}
• {"endpoint_text":"- Observed Ctrough of Pembrolizumab at the End of Cycle 6","definition_or_measurement_approach":"Observed trough concentration at end of Cycle 6 measured by PK sampling."}
• {"endpoint_text":"- Number of Participants Who Experienced an Adverse Event (AE)","definition_or_measurement_approach":"Count of participants with at least one adverse event (safety monitoring and reporting)."}
• {"endpoint_text":"- Number of Participants Who Discontinued Study Treatment Due to an AE","definition_or_measurement_approach":"Count of participants who permanently discontinued study treatment because of an adverse event."}
• {"endpoint_text":"- Progression-Free Survival (PFS) per RECIST 1.1 as Assessed by BICR","definition_or_measurement_approach":"PFS measured per RECIST 1.1 and assessed by blinded independent central review (BICR)."}
• {"endpoint_text":"- Overall Survival (OS)","definition_or_measurement_approach":"Time from randomization to death from any cause."}
• {"endpoint_text":"- Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR","definition_or_measurement_approach":"Duration of tumor response per RECIST 1.1 assessed by BICR."}
• {"endpoint_text":"- Anti-Drug Antibodies (ADAs) Incidence After Administration of Pembrolizumab","definition_or_measurement_approach":"Incidence of anti-drug antibodies measured by ADA assays after administration of pembrolizumab."}

Romania

Latest Decision Or Authorization Date

02-03-2026

Number Of Sites

7

Number Of Participants

75

Poland

Latest Decision Or Authorization Date

26-02-2026

Number Of Sites

5

Number Of Participants

51

Spain

Latest Decision Or Authorization Date

26-02-2026

Number Of Sites

4

Number Of Participants

26

Hungary

Latest Decision Or Authorization Date

25-02-2026

Number Of Sites

7

Number Of Participants

38

France

Latest Decision Or Authorization Date

04-03-2026

Number Of Sites

4

Number Of Participants

25

Primary sponsor

Full Name

Merck Sharp & Dohme LLC

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

PPD Global Central Labs

Name

Perceptive Informatics Inc.

Responsibilities

Central imaging

Name

Pharmaceutical Product Development LLC

Name

Parexel International Corp.

Responsibilities

EUB services (call center and medical services)

Name

Eresearchtechnology Inc.

Name

Almac Clinical Services LLC

Name

Hematogenix Laboratory Services LLC

Third parties

• {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"Central imaging","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Hematogenix Laboratory Services LLC","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Parexel International Corp.","duties_or_roles":"EUB services (call center and medical services)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Services LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}