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Study of Pembrolizumab (MK-3475) Subcutaneous (SC) Versus Pembrolizumab Intravenous (IV) Administered With Platinum Doublet Chemotherapy in Participants With Metastatic Squamous or Nonsquamous Non-Small Cell Lung Cancer (NSCLC) (MK-3475-A86)

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ClinicalTrials.gov Identifier: NCT04956692
Recruitment Status : Recruiting
First Posted : July 9, 2021
Last Update Posted : December 6, 2021
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:

The purpose of this study is to evaluate pembrolizumab (MK-3475) subcutaneous (SC) administration as the first-line therapy in the treatment of metastatic squamous and nonsquamous NSCLC by assessing the pharmacokinetics (PK), safety, and efficacy of pembrolizumab SC injection in combination with standard-of-care chemotherapy. The primary hypothesis of the study is Pembrolizumab SC is noninferior to pembrolizumab intravenous (IV) for Cycle 1 Area Under Curve (AUC) and Cycle 6 minimal concentration (Ctrough) at steady state.

Participants who discontinue study treatment after receiving the first course of 35 administrations of pembrolizumab (approximately up to 2 years) for reasons other than disease progression or intolerability, may be eligible for a second course of pembrolizumab for up to approximately 1 additional year if they have experienced radiographic disease progression per RECIST 1.1 as assessed by BICR after stopping first course treatment.


Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Biological: Pembrolizumab SC Biological: Pembrolizumab IV Drug: Paclitaxel Drug: Nab-Paclitaxel Drug: Carboplatin Drug: Cisplatin Drug: Pemetrexed Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 450 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Phase 3, Open-label Study to Investigate the Pharmacokinetics and Safety of Subcutaneous Pembrolizumab Versus Intravenous Pembrolizumab, Administered With Platinum Doublet Chemotherapy, in the First-Line Treatment of Participants With Metastatic Squamous or Nonsquamous Non-Small-Cell Lung Cancer
Actual Study Start Date : August 5, 2021
Estimated Primary Completion Date : February 10, 2023
Estimated Study Completion Date : October 14, 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy
Participants receive pembrolizumab subcutaneous (SC) administration on Day 1 of each cycle (cycle length = 3 weeks) for up to 35 cycles (up to ~2 years) PLUS paclitaxel IV (on Day 1 of each cycle) OR nab-paclitaxel IV (on Days 1, 8, and 15 of each cycle) and carboplatin IV (on Day 1 of each cycle) for 4 cycles for Squamous NSCLC; PLUS carboplatin IV (on Day 1 of each cycle) Or cisplatin IV (on Day 1 of each cycle) for 4 cycles and pemetrexed IV (on Day 1 of each cycle) until progression, intolerable adverse events, or participant/physician decision for Non-squamous NSCLC.
Biological: Pembrolizumab SC
SC injection

Drug: Paclitaxel
IV injection
Other Names:
  • Nov-Onxol
  • Onxol
  • Paclitaxel Novaplus
  • Taxol

Drug: Nab-Paclitaxel
IV infusion
Other Names:
  • Abraxane
  • Nanoparticle albumin-bound paclitaxel

Drug: Carboplatin
IV infusion
Other Names:
  • Paraplatin
  • Paraplatin NovaPlus

Drug: Cisplatin
IV infusion
Other Name: Platinol-AQ

Drug: Pemetrexed
IV infusion
Other Names:
  • LY231514
  • Alimta
  • Pemetrexed Disodium

Active Comparator: Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy
Participants receive pembrolizumab intravenous (IV) administration on Day 1 of each cycle (cycle length = 3 weeks) for up to 35 cycles (up to ~2 years) PLUS paclitaxel IV (on Day 1 of each cycle) OR nab-paclitaxel IV (on Days 1, 8, and 15 of each cycle) and carboplatin IV (on Day 1 of each cycle) for 4 cycles for Squamous NSCLC; PLUS carboplatin IV (on Day 1 of each cycle) Or cisplatin IV (on Day 1 of each cycle) for 4 cycles and pemetrexed IV (on Day 1 of each cycle) until progression, intolerable adverse events, or participant/physician decision for Non-squamous NSCLC.
Biological: Pembrolizumab IV
IV injection
Other Names:
  • MK-3475
  • KEYTRUDA®
  • SCH 900475

Drug: Paclitaxel
IV injection
Other Names:
  • Nov-Onxol
  • Onxol
  • Paclitaxel Novaplus
  • Taxol

Drug: Nab-Paclitaxel
IV infusion
Other Names:
  • Abraxane
  • Nanoparticle albumin-bound paclitaxel

Drug: Carboplatin
IV infusion
Other Names:
  • Paraplatin
  • Paraplatin NovaPlus

Drug: Cisplatin
IV infusion
Other Name: Platinol-AQ

Drug: Pemetrexed
IV infusion
Other Names:
  • LY231514
  • Alimta
  • Pemetrexed Disodium




Primary Outcome Measures :
  1. Area Under The Curve From 0-3 Weeks (AUC 0-3wks) of Pembrolizumab at Cycle 1 [ Time Frame: Pharmacokinetic (PK) collection at designated timepoints in Cycle 1 (Up to approximately 3 weeks; cycle length = 3 weeks) ]
    AUC0-3wks at Cycle 1 is defined as the area under curve exposure parameter over a 3-week dosing interval in Cycle 1.

  2. Minimal Concentration (Ctrough) of Pembrolizumab at the End of Cycle 6 [ Time Frame: PK collection at end of Cycle 6 (approximately at end of Week 18; cycle length = 3 weeks) ]
    Ctrough of Cycle 6 is defined as the observed trough concentration measured at the end of the dosing interval in Cycle 6.


Secondary Outcome Measures :
  1. Objective Response (OR) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to approximately 5 years ]
    The OR rate is defined as the percentage of participants who achieve a confirmed complete response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by BICR.

  2. Ctrough of Pembrolizumab at the End of Cycle 1 [ Time Frame: PK collection at end of Cycle 1 (approximately at end of Week 3; cycle length = 3 weeks) ]
    Ctrough of Cycle 1 is defined as the observed trough concentration at the end of the dosing interval in Cycle 1.

  3. Maximum Concentration (Cmax) of Pembrolizumab at Cycle 1 [ Time Frame: PK collection at designated timepoints in Cycle 1 (Up to approximately 3 weeks; cycle length = 3 weeks) ]
    Cmax at Cycle 1 is defined as the observed peak concentration over the dosing interval in Cycle 1.

  4. AUC 0-3wks of Pembrolizumab at Cycle 6 [ Time Frame: PK collection at designated timepoints in Cycle 6 (Up to approximately 3 weeks; cycle length = 3 weeks) ]
    AUC0-3wks at Cycle 6 is defined as the area under curve exposure parameter over a 3-week dosing interval in Cycle 6.

  5. Cmax of Pembrolizumab at Cycle 6 [ Time Frame: PK collection at designated timepoints in Cycle 6 (Up to approximately 3 weeks; cycle length = 3 weeks) ]
    Cmax at Cycle 6 is defined as the observed peak concentration over the dosing interval in Cycle 6.

  6. Number of Participants Who Experienced an Adverse Event (AE) [ Time Frame: Up to approximately 28 months ]
    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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experience an AE will be reported.

  7. Number of Participants Who Discontinued Study Treatment Due to an AE [ Time Frame: Up to approximately 25 months ]
    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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. The number of participants who discontinue study treatment due to an AE will be presented.

  8. Progression-Free Survival (PFS) per RECIST 1.1 as Assessed by BICR [ Time Frame: Up to approximately 5 years ]
    PFS is defined as the time from randomization to the first documented PD per RECIST 1.1 by BICR or death due to any cause, whichever occurs first. 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.

  9. Overall Survival (OS) [ Time Frame: Up to approximately 5 years ]
    OS is defined as the time from randomization to death due to any cause.

  10. Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR [ Time Frame: Up to approximately 5 years ]
    For participants who show confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, duration of response is defined as the time from the first documented evidence of CR or PR until disease progression (PD) per RECIST 1.1 by BICR or death due to any cause, whichever occurs first. 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 demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD.

  11. Anti-Drug Antibodies (ADAs) Incidence After Administration of Pembrolizumab [ Time Frame: Up to approximately 26 months ]
    ADA incidence will be assessed by analyzing the development of ADAs following administration of pembrolizumab SC and pembrolizumab IV.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has pathologically (histologically or cytologically) confirmed diagnosis of squamous or nonsquamous non-small cell lung cancer (NSCLC)
  • Has Stage IV (T any, N any, M1a, M1b, or M1c - American Joint Committee on Cancer 8th Edition) squamous or nonsquamous NSCLC
  • Has confirmation that epidermal growth factor receptor (EGFR), Anaplastic lymphoma kinase (ALK), or ROS Proto-Oncogene 1, Receptor Tyrosine Kinase (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
  • 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
  • Has an Eastern Cooperative Oncology Group (ECOG) performance score (PS) of 0 or 1
  • Male participants are eligible to participate if they agree to use contraception as per protocol unless confirmed to be azoospermic
  • 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
  • Has measurable disease per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by the local site investigator/radiology
  • 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
  • Has adequate organ function

Exclusion Criteria:

  • Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
  • Has known central nervous system (ie, 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
  • Has severe hypersensitivity to study intervention and/or any of its excipients
  • Has an active autoimmune disease that has required systemic treatment in past 2 years
  • Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
  • Has an active infection requiring systemic therapy
  • Has a known history of human immunodeficiency virus (HIV) infection and/or Hepatitis B infection or known active Hepatitis C infection
  • Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
  • Has symptomatic ascites or pleural effusion. A participant who is clinically stable after treatment for these conditions is eligible
  • 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
  • Received radiation therapy to the lung that is >30 Gray within 6 months of the first dose of study intervention
  • Is expected to require any other form of antineoplastic therapy while on study
  • 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
  • For participants with nonsquamous histology: Is unable or unwilling to take folic acid or vitamin B12 supplementation
  • Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease
  • Has received a live or live attenuated vaccine within 30 days prior to 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 prior to the first dose of study intervention
  • 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
  • Has had an allogenic tissue/solid organ transplant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04956692


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
Show Show 63 study locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT04956692    
Other Study ID Numbers: 3475-A86
MK-3475-A86 ( Other Identifier: Merck )
2020-002729-27 ( EudraCT Number )
jRCT2021210032 ( Registry Identifier: jRCT (Japan Registry of Clinical Trials) )
First Posted: July 9, 2021    Key Record Dates
Last Update Posted: December 6, 2021
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck Sharp & Dohme Corp.:
Programmed Cell Death 1 (PD1, PD-1)
Programmed Cell Death-Ligand 1 (PDL1, PD-L1)
Programmed Cell Death-Ligand 2 (PDL2, PD-L2)
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Pembrolizumab
Pemetrexed
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors