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NCT Number: NCT05722015

A Study of Subcutaneous (SC) Pembrolizumab Coformulated With Berahyaluronidase Alfa (MK-3475A) vs Intravenous Pembrolizumab in Adult Participants With Metastatic Non-small Cell Lung Cancer (NSCLC) (MK-3475A-D77)

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

Active, not recruiting

This study is active but is not currently recruiting participants.

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Key information

Conditions

Metastatic Non-small Cell Lung Cancer Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Hospital Italiano de Buenos Aires-Clinical Oncology ( Site 1005), Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

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About this study

Effective as of Amendment 4, participants will no longer be able to start a second course of pembrolizumab. Participants already receiving second course treatment at the time of amendment 4 should continue to receive second course treatment.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Pembrolizumab Formulated with Berahyaluronidase Alfa

Biological

Pembrolizumab (+) Berahyaluronidase alfa SC will be administered for squamous and nonsquamous NSCLC as per the schedule specified in arm; participants may have been eligible for second course if they met certain protocol-specified criteria prior to study amendment 4.

Other names: MK-3475A

Pemetrexed

Drug

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

Other names: Alimta

Cisplatin

Drug

Cisplatin 75 mg/m² by IV Infusion will be administered for nonsquamous and squamous NSCLC as per the schedule specified in arm.

Other names: Platinol-AQ

carboplatin

Drug

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.

paclitaxel

Drug

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

Other names: Taxol

Nab-paclitaxel

Drug

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

Other names: Albumin-bound paclitaxel

Pembrolizumab

Biological

Pembrolizumab by IV Infusion will be administered for squamous and nonsquamous NSCLC as per the schedule specified in arm; participants may have been eligible for second course if they met certain protocol-specified criteria prior to study amendment 4.

Other names: MK-3475, KEYTRUDA

Filgrastim

Drug

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

Pegylated filgrastim

Drug

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

Primary outcomes

  1. Cycle 1: Area Under the Curve From Time 0 to 6 Weeks (AUC0-6 Weeks) of Pembrolizumab After the First Dose

    Time frame: Cycle 1: Arm 1: Day 1: Predose and Days 2, 3, 4, 5, 6, 7, 10, 15, 29, and 42 postdose; Arm 2: Day 1: Predose and at the end of infusion, Days 4, 15, 29, and 42 postdose (cycle length = 42 days)

    AUC0-6 weeks was defined as a measure of pembrolizumab exposure that was calculated as the product of serum drug concentration and time from zero to 6 weeks. Blood samples were collected at pre-specified timepoints to determine AUC0-6 weeks. Per protocol, geometric mean AUC0-6 weeks value of pembrolizumab after the first dose of pembrolizumab formulated with berahyaluronidase alfa in arm 1 and after first dose of pembrolizumab in arm 2 was presented.

  2. Cycle 3: Trough Serum Concentration (Ctrough) of Pembrolizumab at Steady State

    Time frame: Cycle 3: Arm 1: Day 1: Predose and Days 4, 10, and 42 postdose; Arm 2: Day 1: Predose and at the end of infusion, Days 4 and 42 postdose (cycle length = 42 days)

    Ctrough was defined as the lowest serum concentration of pembrolizumab reached at steady state. Blood samples were collected at pre-specified timepoints for the determination of Ctrough. Per protocol, geometric mean Ctrough value of pembrolizumab at steady state of pembrolizumab formulated with berahyaluronidase alfa in arm 1 and of pembrolizumab in arm 2 was presented.

Secondary outcomes

  1. Cycle 1: Maximum Serum Concentration (Cmax) of Pembrolizumab After the First Dose

    Time frame: Cycle 1: Arm 1: Day 1: Predose and Days 2, 3, 4, 5, 6, 7, 10, 15, 29, and 42 postdose; Arm 2: Day 1: Predose and at the end of infusion, Days 4, 15, 29, and 42 postdose (cycle length = 42 days)

    Cmax was defined as the maximum serum concentration of pembrolizumab reached after first dose. Blood samples were collected at pre-specified timepoints for the determination of Cmax. Per protocol, geometric mean Cmax value of pembrolizumab after the first dose of pembrolizumab formulated with berahyaluronidase alfa in arm 1 and after first dose of pembrolizumab in arm 2 was presented.

  2. Cycle 1: Trough Serum Concentration (Ctrough) of Pembrolizumab After the First Dose

    Time frame: Cycle 1: Arm 1: Day 1: Predose and Days 2, 3, 4, 5, 6, 7, 10, 15, 29, and 42 postdose; Arm 2: Day 1: Predose and at the end of infusion, Days 4, 15, 29, and 42 postdose (cycle length = 42 days)

    Ctrough was defined as the lowest serum concentration of pembrolizumab reached after first dose. Blood samples were collected at pre-specified timepoints for the determination of Ctrough. Per protocol, geometric mean Ctrough value of pembrolizumab after the first dose of pembrolizumab formulated with berahyaluronidase alfa in arm 1 and after first dose of pembrolizumab in arm 2 was presented.

  3. Cycle 3: Area Under the Curve From Time 0 to 6 Weeks (AUC0-6 Weeks) of Pembrolizumab at Steady State

    Time frame: Cycle 3: Arm 1: Day 1: Predose and Days 4, 10, and 42 postdose; Arm 2: Day 1: Predose and at the end of infusion, Days 4 and 42 postdose (cycle length = 42 days)

    AUC0-6 weeks was defined as a measure of pembrolizumab exposure that was calculated as the product of serum drug concentration and time from zero to 6 weeks. Blood samples were collected at pre-specified timepoints to determine AUC0-6 weeks. Per protocol, geometric mean AUC0-6 weeks value of pembrolizumab at steady state of pembrolizumab formulated with berahyaluronidase alfa in arm 1 and pembrolizumab in arm 2 was presented.

  4. Cycle 3: Maximum Serum Concentration (Cmax) of Pembrolizumab at Steady State

    Time frame: Cycle 3: Arm 1: Day 1: Predose and Days 4, 10, and 42 postdose; Arm 2: Day 1: Predose and at the end of infusion, Days 4 and 42 postdose (cycle length = 42 days)

    Cmax was defined as the maximum serum concentration of pembrolizumab reached at steady state. Blood samples were collected at pre-specified timepoints to determine Cmax. Per protocol, geometric mean Cmax value of pembrolizumab at steady state of pembrolizumab formulated with berahyaluronidase alfa in arm 1 and pembrolizumab in arm 2 was presented.

  5. Number of Participants Who Test Positive for Anti-Drug Antibodies (ADAs) for Pembrolizumab

    Time frame: Predose and Postdose on Day 1 of Cycles 1 through 18 (up to approximately 28 months). Each cycle is 6 weeks.

    Blood samples were collected at designated time points for the determination of the presence or absence of anti-pembrolizumab antibodies. Per protocol, the number of participants who developed anti pembrolizumab antibodies were reported.

  6. Objective Response Rate (ORR)

    Time frame: Up to approximately 28 months

    ORR was defined as the percentage of participants with 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 Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experienced CR or PR as assessed by Blinded Independent Central Review (BICR) were presented.

  7. Progression-free Survival (PFS)

    Time frame: Up to approximately 28 months

    PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by 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 were presented.

  8. Overall Survival (OS)

    Time frame: Up to approximately 28 months

    OS was defined as the time from randomization to death due to any cause.

  9. Duration of Response (DOR)

    Time frame: Up to approximately 28 months

    For participants who demonstrated a 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, DOR is defined as the time from first documented evidence of CR or PR until 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 demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR were presented.

  10. Number of Participants Who Experienced at Least One Adverse Event (AE)

    Time frame: Up to approximately 28 months

    An AE was 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 experienced at least one AE were reported .

  11. Number of Participants Who Discontinued Study Treatment Due to 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. 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 European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire-Core30 (QLQ-C30) Combined Global Health Status/Quality of Life (Items 29 & 30) Scale Combined Score

    Time frame: Baseline and Week 24

    EORTC QLQ-C30 is a questionnaire to assess the overall quality of life (QoL) of cancer patients. Participant responses to questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and QoL ("How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). The combined score of GHS (Item 29) and QoL (Item 30) is computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. Per protocol, the change from baseline in GHS and QoL combined score was presented.

  13. Change From Baseline in Physical Functioning (EORTC-QLQ-C30 Items 1-5) Score

    Time frame: Baseline and Week 24

    EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 5 questions about their physical functioning (Items 1 to 5) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 was computed by averaging the raw scores of the 5 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. Per protocol, the change from baseline in EORTC QLQ-C30 physical functioning (Items 1-5) combined score was presented.

  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 Week 24

    EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to the questions "Were you limited in doing either your work or other daily activities during the past week?" and "Were you limited in pursuing your hobbies or other leisure time activities during the past week?" will be scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 was computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. Higher scores indicate a better level of role functioning. Change from baseline in the EORTC QLQ-C30 role functioning (Items 6-7) combined score was presented.

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study 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

Important dates

Study start
2023
Primary completion
2024
Study completion
2028
First posted
Feb 10, 2023
Registry last updated
Aug 26, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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