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Trial record 1 of 2 for:    3475A-d77
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A Study of Subcutaneous (SC) Pembrolizumab Coformulated With Hyaluronidase (MK-3475A) vs Intravenous Pembrolizumab in Adult Participants With Metastatic Non-small Cell Lung Cancer (NSCLC) (MK-3475A-D77)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05722015
Recruitment Status : Active, not recruiting
First Posted : February 10, 2023
Last Update Posted : February 28, 2024
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Study Description
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Brief Summary:
This study is to assess the pharmacokinetics (PK) and safety of SC MK-3475A vs intravenous (IV) pembrolizumab, administered with chemotherapy in first line treatment of adult participants with metastatic non-small cell lung cancer. The primary hypotheses of this study are MK-3475A subcutaneous (SC) is noninferior to pembrolizumab IV with respect to PK parameters.

Condition or disease Intervention/treatment Phase
Metastatic Non-small Cell Lung Cancer Biological: Pembrolizumab coformulated with hyaluronidase Drug: Pemetrexed Drug: Cisplatin Drug: Carboplatin Drug: Paclitaxel Drug: Nab-paclitaxel Biological: Pembrolizumab Drug: Filgrastim Drug: Pegylated filgrastim Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 378 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3 Randomized, Open-label Clinical Study to Evaluate the Pharmacokinetics and Safety of Subcutaneous Pembrolizumab Coformulated With Hyaluronidase (MK-3475A) Versus Intravenous Pembrolizumab, Administered With Chemotherapy, in the First-line Treatment of Participants With Metastatic Non-small Cell Lung Cancer
Actual Study Start Date : February 14, 2023
Estimated Primary Completion Date : September 23, 2024
Estimated Study Completion Date : May 22, 2028

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm 1 (MK-3475A + Platinum Doublet Chemotherapy)
Participants with treatment-naïve metastatic NSCLC will receive MK 3475A SC in combination with platinum doublet chemotherapy.
 Biological: Pembrolizumab coformulated with hyaluronidase
MK3475A SC will be administered for squamous and nonsquamous NSCLC as per the schedule specified in arm; participants may be eligible for second course.
Other Name: MK-3475A

Drug: Pemetrexed
Pemetrexed 500 mg/m² by IV Infusion will be administered for nonsquamous NSCLC as per the schedule specified in arm.
Other Name: Alimta

Drug: Cisplatin
Cisplatin 75 mg/m² by IV Infusion will be administered for nonsquamous and squamous NSCLC as per the schedule specified in arm.
Other Name: Platinol-AQ

Drug: Carboplatin
Carboplatin AUC 5 mg/mL/min in nonsquamous and AUC 6 mg/mL/min in squamous NSCLC will be administered as per the schedule specified in arm.

Drug: Paclitaxel
Paclitaxel 200 mg/m² by IV Infusion will be administered for squamous NSCLC as per the schedule specified in arm.
Other Name: Taxol

Drug: Nab-paclitaxel
Nab-paclitaxel 100 mg/m² by IV Infusion will be administered for squamous NSCLC as per the schedule specified in arm.
Other Name: Albumin-bound paclitaxel

Drug: Filgrastim
Filgrastim will be administered as per the schedule specified for the arm.

Drug: Pegylated filgrastim
Pegylated filgrastim will be administered as per the schedule specified for the arm.
Active Comparator: Arm 2 (Pembrolizumab + Platinum Doublet Chemotherapy)
Participants with treatment-naïve metastatic NSCLC will receive Pembrolizumab IV in combination with platinum doublet chemotherapy.
 Drug: Pemetrexed
Pemetrexed 500 mg/m² by IV Infusion will be administered for nonsquamous NSCLC as per the schedule specified in arm.
Other Name: Alimta

Drug: Cisplatin
Cisplatin 75 mg/m² by IV Infusion will be administered for nonsquamous and squamous NSCLC as per the schedule specified in arm.
Other Name: Platinol-AQ

Drug: Carboplatin
Carboplatin AUC 5 mg/mL/min in nonsquamous and AUC 6 mg/mL/min in squamous NSCLC will be administered as per the schedule specified in arm.

Drug: Paclitaxel
Paclitaxel 200 mg/m² by IV Infusion will be administered for squamous NSCLC as per the schedule specified in arm.
Other Name: Taxol

Drug: Nab-paclitaxel
Nab-paclitaxel 100 mg/m² by IV Infusion will be administered for squamous NSCLC as per the schedule specified in arm.
Other Name: Albumin-bound paclitaxel

Biological: Pembrolizumab
Pembrolizumab by IV Infusion will be administered for squamous and nonsquamous NSCLC as per the schedule specified in arm; participants may be eligible for second course.
Other Name: MK-3475, KEYTRUDA

Drug: Filgrastim
Filgrastim will be administered as per the schedule specified for the arm.

Drug: Pegylated filgrastim
Pegylated filgrastim will be administered as per the schedule specified for the arm.


Outcome Measures
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Primary Outcome Measures :
  1. Area Under the Curve (AUC) of Pembrolizumab Measured After the First Dose [ Time Frame: At designated time points (Up to ~14 months). ]
    AUC is defined as area under curve exposure. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine AUC.

  2. Trough Concentration (Ctrough) of Pembrolizumab Measured at Steady State [ Time Frame: At designated time points (Up to ~18 months) ]
    Ctrough is defined as the trough concentration at steady-state. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Ctrough.


Secondary Outcome Measures :
  1. Maximum Serum Concentration (Cmax) of Pembrolizumab Measured After the First Dose [ Time Frame: At designated time points (Up to ~28 months) ]
    Cmax is defined as the peak concentration over the dosing interval. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmax.

  2. Trough Concentration (Ctrough) of Pembrolizumab Measured After the First Dose [ Time Frame: At designated time points (Up to ~28 months) ]
    Ctrough is defined as the trough concentration. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Ctrough.

  3. Area Under the Curve (AUC) of Pembrolizumab Measured at Steady State [ Time Frame: At designated time points (Up to ~28 months) ]
    AUC is defined as area under curve exposure at steady state. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine AUC.

  4. Maximum Serum Concentration (Cmax) of Pembrolizumab Measured at Steady State [ Time Frame: At designated time points (Up to ~28 months) ]
    Cmax is defined as the peak concentration over the dosing interval in steady-state. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmax

  5. Number of Participants Who Test Positive for Anti-Drug Antibodies (ADAs) for Pembrolizumab [ Time Frame: At designated time points (Up to ~28 months) ]
    Blood samples are to be collected at designated time points for the determination of the presence or absence of anti-pembrolizumab antibodies. The percentage of participants who develop anti pembrolizumab antibodies will be reported.

  6. Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Up to~60 months ]
    The ORR is defined as the percentage of participants who achieve a confirmed CR or PR per RECIST 1.1 as assessed by BICR.

  7. Progression-free Survival (PFS) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Up to~60 months ]
    PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 by BICR or death due to any cause, whichever occurs first.

  8. Overall Survival (OS) [ Time Frame: Up to~60 months ]
    OS is defined as the time from randomization to death due to any cause.

  9. Duration of Response (DOR) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Up to~60 months ]
    For participants who show confirmed CR or PR, DOR is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.

  10. Number of Participants Who Experienced at Least One Adverse Event (AE) [ Time Frame: Up to~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. The number of participants with an AE will be reported for Arms 1 and 2.

  11. Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) [ Time Frame: Up to~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. The number of participants who discontinue study treatment due to an AE will be reported for Arms 1 and 2.

  12. Change From Baseline in the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) Global Health Status/Quality of Life (GHS/QoL) Score-Items 29 and 30 [ Time Frame: Baseline and up to ~28 months ]
    EORTC QLQ-C30 is a psychometrically and clinically validated instrument appropriate for assessing HRQoL in oncology studies. The EORTC QLQ-C30 is the most widely used cancer-specific HRQoL instrument, which contains 30 items and measures 5 functional dimensions (physical, role, emotional, cognitive and social), 3 symptom items (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial impact), and a global health and QoL scale. For the global health status or QoL and function scales, a higher value indicates a better level of function; for symptom scales and items, a higher value indicates increased severity of symptoms.

  13. Change From Baseline in the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) Physical Functioning Score-Items 1 to 5 [ Time Frame: Baseline and up to ~28 months ]
    The EQ-5D-5L is a standardized instrument for use as a measure of health outcome and will provide data to develop health utilities for use in health economic analyses. The 5 health state dimensions in the EQ-5D-5L include the following: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension is rated on a 5-point scale from 1 (no problem) to 5 (unable to/extreme problems). The EQ-5D-5L also includes a graded (0 to 100) vertical visual analog scale on which the participant rates his or her general state of health at the time of the assessment. This instrument has been used extensively in cancer studies and published results from these studies support its validity and reliability.

  14. Change From Baseline in the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) Role Functioning Score-Items 6 and 7 [ Time Frame: Baseline and up to ~28 months ]
    The EQ-5D-5L is a standardized instrument for use as a measure of health outcome and will provide data to develop health utilities for use in health economic analyses. The 5 health state dimensions in the EQ-5D-5L include the following: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension is rated on a 5-point scale from 1 (no problem) to 5 (unable to/extreme problems). The EQ-5D-5L also includes a graded (0 to 100) vertical visual analog scale on which the participant rates his or her general state of health at the time of the assessment. This instrument has been used extensively in cancer studies and published results from these studies support its validity and reliability.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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

The key inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

  • Has histologically or cytologically confirmed diagnosis of squamous or non-squamous Non-small Cell Lung Cancer (NSCLC).
  • Must provide archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated.
  • Has a life expectancy of at least 3 months.

Exclusion Criteria:

  • Has a diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements.
  • Has received prior systemic anticancer therapy for metastatic NSCLC.
  • Has received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.
  • Has received prior radiotherapy within 2 weeks of start of study intervention or has radiation-related toxicity requiring corticosteroids.
  • Has received radiation therapy to the lung (>30 Gray) within 6 months of start of study intervention.
  • Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy.
  • Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
  • Has an active autoimmune disease that has required systemic treatment in past 2 years.
  • Has an active infection requiring systemic therapy.
  • Has a history of human immunodeficiency virus (HIV) infection.
  • Has a history of Hepatitis B or C.
  • Has not adequately recovered from major surgery or has ongoing surgical complications.
  • Has a history of allogenic tissue/solid organ transplant.
Contacts and Locations
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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): NCT05722015


Locations
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Sponsors and Collaborators
Merck Sharp & Dohme LLC
Investigators
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Study Director: Medical Director Merck Sharp & Dohme LLC
More Information
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Additional Information:

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Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT05722015    
Other Study ID Numbers: 3475A-D77
2022-501506-36-00 ( Other Identifier: EU CT )
MK-3475A-D77 ( Other Identifier: Secondary Id )
jRCT2031230049 ( Registry Identifier: Japan Registry of Clinical Trials (jRCT) )
First Posted: February 10, 2023    Key Record Dates
Last Update Posted: February 28, 2024
Last Verified: February 2024
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
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
 Lenograstim
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors