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)

• ClinicalTrials.gov Identifier: NCT05722015
• Recruitment Status: Active, not recruiting
• First Posted: February 10, 2023
• Last Update Posted: February 28, 2024
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Tracking Information

• First Submitted Date: January 27, 2023
• First Posted Date: February 10, 2023
• Last Update Posted Date: February 28, 2024
• Actual Study Start Date: February 14, 2023
• Estimated Primary Completion Date: September 23, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 25, 2023)

• 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.
• 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.

Original Primary Outcome Measures (submitted: January 27, 2023)

• Area Under the Curve (AUC) of Pembrolizumab Measured After the First Dose [ Time Frame: At pre-defined intervals from first administration of study drug up to treatment discontinuation visit (up to approximately 27 months) ]
  AUC is defined as area under curve exposure.
• Trough Concentration (Ctrough) of Pembrolizumab Measured at Steady State [ Time Frame: At pre-defined intervals from first administration of study drug up to treatment discontinuation visit (up to approximately 27 months) ]
  Ctrough is defined as the trough concentration at steady-state.

Current Secondary Outcome Measures (submitted: April 25, 2023)

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

Original Secondary Outcome Measures (submitted: January 27, 2023)

• Maximum Serum Concentration (Cmax) of Pembrolizumab Measured After the First Dose [ Time Frame: At pre-defined intervals from first administration of study drug up to treatment discontinuation visit (up to approximately 27 months) ]
  Cmax is defined as the peak concentration over the dosing interval.
• Trough Concentration (Ctrough) of Pembrolizumab Measured After the First Dose [ Time Frame: At pre-defined intervals from first administration of study drug up to treatment discontinuation visit (up to approximately 27 months) ]
  Ctrough is defined as the trough concentration.
• Area Under the Curve (AUC) of Pembrolizumab Measured at Steady State [ Time Frame: At pre-defined intervals from first administration of study drug up to treatment discontinuation visit (up to approximately 27 months) ]
  AUC is defined as area under curve exposure at steady state.
• Maximum Serum Concentration (Cmax) of Pembrolizumab Measured at Steady State [ Time Frame: At pre-defined intervals from first administration of study drug up to treatment discontinuation visit (up to approximately 27 months) ]
  Cmax is defined as the peak concentration over the dosing interval in steady-state.
• Number of Participants Who Test Positive for Anti-Drug Antibodies (ADAs) for Pembrolizumab [ Time Frame: At pre-defined intervals from first administration of study drug up to treatment discontinuation visit (up to approximately 27 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.
• 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.
• 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.
• Overall Survival (OS) [ Time Frame: Up to~60 months ]
  OS is defined as the time from randomization to death due to any cause.
• 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.
• Number of Participants Who Experienced at Least One Adverse Event (AE) [ Time Frame: Up to~29 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.
• Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) [ Time Frame: Up to~27 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.
• 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 ~27 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.
• 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 ~27 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.
• 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 ~27 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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Non-small Cell Lung Cancer

Intervention

• 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
• 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.

Study Arms

• 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.
  Interventions:

  • Biological: Pembrolizumab coformulated with hyaluronidase
  • Drug: Pemetrexed
  • Drug: Cisplatin
  • Drug: Carboplatin
  • Drug: Paclitaxel
  • Drug: Nab-paclitaxel
  • Drug: Filgrastim
  • Drug: Pegylated filgrastim
• Active Comparator: Arm 2 (Pembrolizumab + Platinum Doublet Chemotherapy)
  Participants with treatment-naïve metastatic NSCLC will receive Pembrolizumab IV in combination with platinum doublet chemotherapy.
  Interventions:

  • Drug: Pemetrexed
  • Drug: Cisplatin
  • Drug: Carboplatin
  • Drug: Paclitaxel
  • Drug: Nab-paclitaxel
  • Biological: Pembrolizumab
  • Drug: Filgrastim
  • Drug: Pegylated filgrastim

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: February 26, 2024): 378
• Original Estimated Enrollment (submitted: January 27, 2023): 339
• Estimated Study Completion Date: May 22, 2028
• Estimated Primary Completion Date: September 23, 2024 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Brazil, Chile, China, France, Guatemala, Hungary, Japan, Poland, Romania, South Africa, Spain, Taiwan, Thailand, Turkey, United States

Administrative Information

• NCT Number: 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) )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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

• Current Responsible Party: Merck Sharp & Dohme LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Merck Sharp & Dohme LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Merck Sharp & Dohme LLC
• Verification Date: February 2024