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Active, not recruitingNCT05722015Updated Aug 26, 2026Results posted

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)

A Phase 3 interventional study of Pembrolizumab Formulated with Berahyaluronidase Alfa and Pemetrexed in Metastatic Non-small Cell Lung Cancer, sponsored by Merck Sharp & Dohme LLC. Active, not recruiting at 110 sites in 16 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-26.

Sponsored by Merck Sharp & Dohme LLC · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
377
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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.

Read the detailed description

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.

02

Conditions studied

  • Metastatic Non-small Cell Lung Cancer
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

Inclusion criteria

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

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
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
377 participants (actual)

Study arms

  • Experimental
    Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy

    Participants with treatment-naïve metastatic NSCLC receive 790 mg of Pembrolizumab Formulated With Berahyaluronidase Alfa via subcutaneous (SC) injection on Day 1 of each 6-week cycle for 18 cycles (up to approximately 108 weeks) in combination with platinum doublet chemotherapy.

    Biological: Pembrolizumab Formulated with Berahyaluronidase Alfa · 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 receive 400 mg pembrolizumab intravenous (IV) infusion in combination with platinum doublet chemotherapy.

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

Interventions

  • BiologicalPembrolizumab Formulated with Berahyaluronidase Alfa

    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.

    Also known as: MK-3475A

  • DrugPemetrexed

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

    Also known as: Alimta

  • DrugCisplatin

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

    Also known as: Platinol-AQ

  • DrugCarboplatin

    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.

  • DrugPaclitaxel

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

    Also known as: Taxol

  • DrugNab-paclitaxel

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

    Also known as: Albumin-bound paclitaxel

  • BiologicalPembrolizumab

    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.

    Also known as: MK-3475, KEYTRUDA

  • DrugFilgrastim

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

  • DrugPegylated filgrastim

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

05

What researchers measure

Primary outcomes

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

    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.

    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)

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

    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.

    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)

Secondary outcomes

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

    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.

    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)

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

    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.

    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)

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

    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.

    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)

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

    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.

    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)

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

    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.

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

  6. Objective Response Rate (ORR)

    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.

    Time frame: Up to approximately 28 months

  7. Progression-free Survival (PFS)

    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.

    Time frame: Up to approximately 28 months

  8. Overall Survival (OS)

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

    Time frame: Up to approximately 28 months

  9. Duration of Response (DOR)

    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.

    Time frame: Up to approximately 28 months

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

    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 .

    Time frame: Up to approximately 28 months

  11. Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)

    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.

    Time frame: Up to approximately 28 months

  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

    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.

    Time frame: Baseline and Week 24

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

    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.

    Time frame: Baseline and Week 24

  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

    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.

    Time frame: Baseline and Week 24

06

Results

Posted Jul 28, 2025

Participant flow

Participant flow — Overall Study
MilestoneArm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet ChemotherapyArm 2: Pembrolizumab + Platinum Doublet Chemotherapy
Started251126
Completed00
Not completed251126
Withdrew: Death5737
Withdrew: Lost to follow-up10
Withdrew: Withdrawal by subject51
Withdrew: Participants ongoing18888

Outcome measures

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

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.

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)
Reported as:
Geometric mean · μg·day/mL
Cycle 1: Area Under the Curve From Time 0 to 6 Weeks (AUC0-6 Weeks) of Pembrolizumab After the First Dose
μg·day/mLArm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet ChemotherapyArm 2: Pembrolizumab + Platinum Doublet Chemotherapy
Cycle 1: Area Under the Curve From Time 0 to 6 Weeks (AUC0-6 Weeks) of Pembrolizumab After the First Dose1633.24 ± 40.411437.58 ± 26.23
Statistical analysis
  • Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy vs Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy · Welch's t test · p = <0.00001 · Geometric mean ratio (gmr): 1.14 · 96% CI 1.06 to 1.22GMR was calculated as the ratio of geometric mean (GM) of Cycle 1 AUC0-6 weeks in Arm 1 to that of Arm 2. The associated 96% confidence interval (CI) were calculated using Welch's t test.
PrimaryCycle 3: Trough Serum Concentration (Ctrough) of Pembrolizumab at Steady State

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.

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)
Reported as:
Geometric mean · μg/mL
Cycle 3: Trough Serum Concentration (Ctrough) of Pembrolizumab at Steady State
μg/mLArm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet ChemotherapyArm 2: Pembrolizumab + Platinum Doublet Chemotherapy
Cycle 3: Trough Serum Concentration (Ctrough) of Pembrolizumab at Steady State39.23 ± 43.2923.49 ± 44.23
Statistical analysis
  • Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy vs Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy · Welch's t test · p = <0.00001 · Gmr: 1.67 · 94% CI 1.52 to 1.84GMR was calculated as the ratio of GM of Cycle 3 Ctrough in Arm 1 to that of Arm 2. The associated 94% CI were calculated using Welch's t test.
SecondaryCycle 1: Maximum Serum Concentration (Cmax) of Pembrolizumab After the First Dose

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.

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)
Reported as:
Geometric mean · μg/mL
Cycle 1: Maximum Serum Concentration (Cmax) of Pembrolizumab After the First Dose
μg/mLArm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet ChemotherapyArm 2: Pembrolizumab + Platinum Doublet Chemotherapy
Cycle 1: Maximum Serum Concentration (Cmax) of Pembrolizumab After the First Dose64.88 ± 44129.7 ± 20.8
SecondaryCycle 1: Trough Serum Concentration (Ctrough) of Pembrolizumab After the First Dose

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.

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)
Reported as:
Geometric mean · μg/mL
Cycle 1: Trough Serum Concentration (Ctrough) of Pembrolizumab After the First Dose
μg/mLArm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet ChemotherapyArm 2: Pembrolizumab + Platinum Doublet Chemotherapy
Cycle 1: Trough Serum Concentration (Ctrough) of Pembrolizumab After the First Dose19.36 ± 52.212.26 ± 50.8
SecondaryCycle 3: Area Under the Curve From Time 0 to 6 Weeks (AUC0-6 Weeks) of Pembrolizumab at Steady State

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.

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)
Reported as:
Geometric mean · μg·day/mL
Cycle 3: Area Under the Curve From Time 0 to 6 Weeks (AUC0-6 Weeks) of Pembrolizumab at Steady State
μg·day/mLArm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet ChemotherapyArm 2: Pembrolizumab + Platinum Doublet Chemotherapy
Cycle 3: Area Under the Curve From Time 0 to 6 Weeks (AUC0-6 Weeks) of Pembrolizumab at Steady State2798 ± 35.52122 ± 27.8
SecondaryCycle 3: Maximum Serum Concentration (Cmax) of Pembrolizumab at Steady State

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.

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)
Reported as:
Geometric mean · μg/mL
Cycle 3: Maximum Serum Concentration (Cmax) of Pembrolizumab at Steady State
μg/mLArm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet ChemotherapyArm 2: Pembrolizumab + Platinum Doublet Chemotherapy
Cycle 3: Maximum Serum Concentration (Cmax) of Pembrolizumab at Steady State98.96 ± 36.8148 ± 21.6
SecondaryNumber of Participants Who Test Positive for Anti-Drug Antibodies (ADAs) for Pembrolizumab

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.

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

Results for this outcome have not been posted.

SecondaryObjective Response Rate (ORR)

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.

Time frame:
Up to approximately 28 months

Results for this outcome have not been posted.

SecondaryProgression-free Survival (PFS)

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.

Time frame:
Up to approximately 28 months

Results for this outcome have not been posted.

SecondaryOverall Survival (OS)

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

Time frame:
Up to approximately 28 months

Results for this outcome have not been posted.

SecondaryDuration of Response (DOR)

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.

Time frame:
Up to approximately 28 months

Results for this outcome have not been posted.

SecondaryNumber of Participants Who Experienced at Least One Adverse Event (AE)

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 .

Time frame:
Up to approximately 28 months

Results for this outcome have not been posted.

SecondaryNumber of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)

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.

Time frame:
Up to approximately 28 months

Results for this outcome have not been posted.

SecondaryChange 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

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.

Time frame:
Baseline and Week 24

Results for this outcome have not been posted.

SecondaryChange From Baseline in Physical Functioning (EORTC-QLQ-C30 Items 1-5) Score

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.

Time frame:
Baseline and Week 24

Results for this outcome have not been posted.

SecondaryChange 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

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.

Time frame:
Baseline and Week 24

Results for this outcome have not been posted.

Adverse events

Collected over Up to approximately 16 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy61/251 (24.3%)98/251 (39%)236/251 (94%)
Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy37/126 (29.4%)51/126 (40.5%)123/126 (97.6%)
Most frequent serious events
Showing 10 of 113
Most frequent serious events
EventArm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet ChemotherapyArm 2: Pembrolizumab + Platinum Doublet Chemotherapy
PneumoniaInfections and infestations25/25113/126
AnaemiaBlood and lymphatic system disorders3/2516/126
Febrile neutropeniaBlood and lymphatic system disorders10/2512/126
ThrombocytopeniaBlood and lymphatic system disorders10/2513/126
NeutropeniaBlood and lymphatic system disorders7/2512/126
Pulmonary embolismRespiratory, thoracic and mediastinal disorders2/2513/126
DeathGeneral disorders4/2511/126
Adrenal insufficiencyEndocrine disorders1/2512/126
FatigueGeneral disorders1/2512/126
Oedema peripheralGeneral disorders0/2512/126
Most frequent other events
Showing 10 of 42
Most frequent other events
EventArm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet ChemotherapyArm 2: Pembrolizumab + Platinum Doublet Chemotherapy
AnaemiaBlood and lymphatic system disorders146/25185/126
NeutropeniaBlood and lymphatic system disorders105/25140/126
LeukopeniaBlood and lymphatic system disorders74/25133/126
ThrombocytopeniaBlood and lymphatic system disorders71/25135/126
NauseaGastrointestinal disorders63/25130/126
Decreased appetiteMetabolism and nutrition disorders28/25127/126
Aspartate aminotransferase increasedInvestigations47/25118/126
ConstipationGastrointestinal disorders35/25123/126
Alanine aminotransferase increasedInvestigations44/25118/126
FatigueGeneral disorders40/25117/126

Baseline characteristics

All randomized participants.

Age, Continuous
Age, Continuous(Years)Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet ChemotherapyArm 2: Pembrolizumab + Platinum Doublet ChemotherapyTotal
Mean64.7 ± 9.664.8 ± 8.564.8 ± 9.2
Sex: Female, Male
Sex: Female, Male(Participants)Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet ChemotherapyArm 2: Pembrolizumab + Platinum Doublet ChemotherapyTotal
Female6940109
Male18286268
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet ChemotherapyArm 2: Pembrolizumab + Platinum Doublet ChemotherapyTotal
Hispanic or Latino7441115
Not Hispanic or Latino17785262
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet ChemotherapyArm 2: Pembrolizumab + Platinum Doublet ChemotherapyTotal
American Indian or Alaska Native246
Asian7436110
Native Hawaiian or Other Pacific Islander000
Black or African American5510
White15878236
More than one race12315
Unknown or Not Reported000
07

Study locations

110 sites
  • St. Joseph's Hospital and Medical Center-Dignity Health Cancer Institute ( Site 0023)
    Phoenix, Arizona 85004, United States
  • Clermont Oncology Center ( Site 0018)
    Clermont, Florida 34711, United States
  • Mid Florida Hematology and Oncology Center ( Site 0010)
    Orange City, Florida 32763, United States
  • University of Illinois at Chicago-University of Illinois Cancer Center ( Site 0022)
    Chicago, Illinois 60612, United States
  • Orchard Healthcare Research Inc. ( Site 0011)
    Skokie, Illinois 60077, United States
  • Franciscan Health Lafayette East ( Site 0020)
    Lafayette, Indiana 47905, United States
  • Mercy Health-Paducah Cancer Center ( Site 0006)
    Paducah, Kentucky 42003, United States
  • Hattiesburg Clinic Hematology/Oncology ( Site 0008)
    Hattiesburg, Mississippi 39401, United States
  • Central Care Cancer Center - Bolivar ( Site 0017)
    Bolivar, Missouri 65613, United States
  • Hospital Italiano de Buenos Aires-Clinical Oncology ( Site 1005)
    Ciudad Autonoma de Buenos Aires, Buenos Aires C1199ABB, Argentina
  • Instituto de Investigaciones Clínicas Mar del Plata ( Site 1001)
    Mar del Plata, Buenos Aires B7600FZO, Argentina
  • Instituto Argentino de Diagnóstico y Tratamiento (IADT) ( Site 1002)
    Buenos Aires, Buenos Aires F.D. C1122AAL, Argentina
  • Instituto Alexander Fleming ( Site 1008)
    Buenos Aires, Buenos Aires F.D. C1426ANZ, Argentina
  • Clinica Adventista Belgrano-Oncology ( Site 1004)
    Buenos Aires, Buenos Aires F.D. C1430EGF, Argentina
  • Sanatorio Parque ( Site 1003)
    Rosario, Santa Fe Province S2000DVC, Argentina
  • Hospital Italiano de Córdoba ( Site 1000)
    Córdoba, X5004BAL, Argentina
  • CRIO - CENTRO REGIONAL INTEGRADO DE ONCOLOGIA-Pesquisa Clínica ( Site 1102)
    Fortaleza, Ceará 60336-232, Brazil
  • Hospital de Cancer de Pernambuco ( Site 1107)
    Recife, Pernambuco 50040-000, Brazil
  • Hospital Nossa Senhora da Conceição-Centro Integrado de Pesquisa em Oncologia ( Site 1100)
    Porto Alegre, Rio Grande do Sul 91350-200, Brazil
  • Instituto Joinvilense de Hematologia e Oncologia ( Site 1101)
    Joinville, Santa Catarina 89201-260, Brazil
  • A. C. Camargo Cancer Center ( Site 1106)
    São Paulo, 01509-010, Brazil
  • IC La Serena Research ( Site 1207)
    La Serena, Coquimbo Region 1720430, Chile
  • Oncocentro Valdivia ( Site 1201)
    Valdivia, Los Ríos Region 5112129, Chile
  • FALP-UIDO ( Site 1203)
    Santiago, Region M. de Santiago 7500921, Chile
  • Oncovida ( Site 1209)
    Santiago, Region M. de Santiago 7500994, Chile
  • Pontificia Universidad Catolica de Chile-Hemato-Oncology ( Site 1210)
    Santiago, Region M. de Santiago 8330024, Chile
  • Instituto Nacional del Cancer-CR Investigación ( Site 1211)
    Santiago, Region M. de Santiago 8380455, Chile
  • Bradfordhill-Clinical Area ( Site 1202)
    Santiago, Region M. de Santiago 8420383, Chile
  • Anhui Provincial Hospital-Cancer Chemotherapy Department ( Site 4503)
    Hefei, Anhui 230071, China
  • Beijing Cancer hospital-intrathoratic deparmtment II ( Site 4510)
    Beijing, Beijing Municipality 100142, China
  • Beijing Peking Union Medical College Hospital-pneumology department ( Site 4501)
    Beijing, Beijing Municipality 100730, China
  • Beijing Chest Hospital,Capital Medical University ( Site 4511)
    Beijing, Beijing Municipality 101149, China
  • Chongqing University Three Gorges Hospital ( Site 4516)
    Wanzhou, Chongqing Municipality 404199, China
  • Fujian Provincial Cancer Hospital ( Site 4517)
    Fuzhou, Fujian 350014, China
  • Southern Medical University Nanfang Hospital-Depatrment of Respiratory and Critical Care Medicine ( Site 4519)
    Guangzhou, Guangdong 510515, China
  • Jiangmen Center Hospital ( Site 4509)
    Jiangmen, Guangdong 529030, China
  • ShenZhen People's Hospital ( Site 4504)
    Shenzhen, Guangdong 518020, China
  • Union Hospital Tongji Medical College Huazhong University of Science and Technology-Medical Oncology ( Site 4502)
    Wuhan, Hubei 430048, China
  • The First Affiliated Hospital of Nanchang University-Respiratory Medicine Department ( Site 4515)
    Nanchang, Jiangxi 330006, China
  • The First Affiliated Hospital of Xi'an Jiaotong University ( Site 4520)
    Xi'an, Shaanxi 710061, China
  • Fudan University Shanghai Cancer Center-Oncology ( Site 4512)
    Shanghai, Shanghai Municipality 200032, China
  • Shanxi Cancer Hospital ( Site 4521)
    Taiyuan, Shanxi 410013, China
  • Tianjin Chest Hospital ( Site 4518)
    Tianjin, Tianjin Municipality 300051, China
  • The First Affiliated Hospital, Zhejiang University-Respiratory Department ( Site 4514)
    Hangzhou, Zhejiang 310003, China
  • Taizhou Hospital of Zhejiang Province ( Site 4508)
    Linhai, Zhejiang 317000, China
  • Centre Hospitalier de Cornouaille Quimper - Concarneau ( Site 2600)
    Quimper, Finistere 29107, France
  • Centre Hospitalier Régional Universitaire de Tours - Hôpital Bretonneau ( Site 2602)
    Tours, Indre-et-Loire 37000, France
  • Hopitaux Universitaires Paris Centre-Hopital Cochin ( Site 2603)
    Paris, 75014, France
  • MEDI-K ( Site 1403)
    Guatemala City, 01009, Guatemala
  • Private Practice- Dr. Rixci Augusto Lenin Ramírez ( Site 1404)
    Guatemala City, 01010, Guatemala
  • Centro Regional de Sub Especialidades Médicas SA ( Site 1401)
    Quetzaltenango, 09001, Guatemala
  • Centro Medico Integral De Cancerología (CEMIC) ( Site 1400)
    Quetzaltenango, 09002, Guatemala
  • Bacs-Kiskun Megyei Korhaz-Onkoradiologiai Kozpont ( Site 2102)
    Kecskemét, Bács-Kiskun county 6000, Hungary
  • Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Onkologiai Kozpont ( Site 2103)
    Szolnok, Jász-Nagykun-Szolnok 5004, Hungary
  • Reformatus Pulmonologiai Centrum ( Site 2105)
    Törökbálint, Pest County 2045, Hungary
  • Semmelweis Egyetem-Pulmonológiai Klinika ( Site 2104)
    Budapest, 1083, Hungary
  • Országos Korányi Pulmonológiai Intézet-VI. Tüdöbelosztály és Bronchológia ( Site 2100)
    Budapest, 1121, Hungary
  • Fujita Health University Hospital ( Site 4406)
    Toyoake, Aichi-ken 470-1192, Japan
  • Kurume University Hospital ( Site 4412)
    Kurume, Fukuoka 830-0011, Japan
  • Gunma Prefectural Cancer Center ( Site 4416)
    Ōta, Gunma 373-8550, Japan
  • National Hospital Organization Hokkaido Cancer Center ( Site 4415)
    Sapporo, Hokkaido 003-0804, Japan
  • Kanagawa Cardiovascular and Respiratory Center ( Site 4404)
    Yokohama, Kanagawa 236-0051, Japan
  • Miyagi Cancer Center ( Site 4401)
    Natori-shi, Miyagi 981-1293, Japan
  • Sendai Kousei Hospital ( Site 4400)
    Sendai, Miyagi 981-0914, Japan
  • Kurashiki Central Hospital ( Site 4409)
    Kurashiki, Okayama-ken 710-8602, Japan
  • Kansai Medical University Hospital ( Site 4408)
    Hirakata, Osaka 573-1191, Japan
  • Osaka Medical and Pharmaceutical University Hospital ( Site 4414)
    Takatsuki, Osaka 569-8686, Japan
  • Saitama Prefectural Cancer Center ( Site 4402)
    Kitaadachi-gun, Saitama 362-0806, Japan
  • Shizuoka Cancer Center ( Site 4405)
    Sunto-gun,, Shizuoka 411-8777, Japan
  • Tochigi Cancer Center ( Site 4417)
    Utsunomiya, Tochigi 320-0834, Japan
  • Juntendo University Hospital ( Site 4413)
    Bunkyo-ku, Tokyo 113-8431, Japan
  • National Hospital Organization Kyushu Medical Center ( Site 4411)
    Fukuoka, 810-8563, Japan
  • National Hospital Organization Kyushu Cancer Center ( Site 4410)
    Fukuoka, 811-1395, Japan
  • Osaka International Cancer Institute ( Site 4407)
    Osaka, 541-8567, Japan
  • Nippon Medical School Hospital ( Site 4403)
    Tokyo, 113-8603, Japan
  • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Klatki Pier ( Site 2800)
    Warsaw, Masovian Voivodeship 02-781, Poland
  • Warmińsko - Mazurskie Centrum Chorób Płuc w Olsztynie-Oddzial Onkologii z Pododdzialem Chemioterapii ( Site 2802)
    Olsztyn, Warmian-Masurian Voivodeship 10-357, Poland
  • Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 2801)
    Koszalin, West Pomeranian Voivodeship 75-581, Poland
  • SC Radiotherapy Center Cluj SRL-Oncologie Medicala ( Site 2303)
    Florești, Cluj 407280, Romania
  • Centrul de Oncologie Sfantul Nectarie-Medical ( Site 2301)
    Craiova, Dolj 200542, Romania
  • Cabinet Medical Oncomed ( Site 2305)
    Timișoara, Timiș County 300239, Romania
  • Institutul Oncologic-Oncologie Medicala ( Site 2302)
    Cluj-Napoca, 400015, Romania
  • CANCERCARE LANGENHOVEN DRIVE ONCOLOGY CENTRE ( Site 2903)
    Port Elizabeth, Eastern Cape 6055, South Africa
  • Medical Oncology Centre of Rosebank ( Site 2907)
    Johannesburg, Gauteng 2196, South Africa
  • Steve Biko Academic Hospital-Medical Oncology ( Site 2904)
    Pretoria, Gauteng 0001, South Africa
  • Sandton Oncology Medical Group (Pty) Ltd-Research ( Site 2900)
    Sandton, Gauteng 2196, South Africa
  • The Oncology Centre ( Site 2901)
    Durban, KwaZulu-Natal 4091, South Africa
  • Cape Town Oncology Trials ( Site 2902)
    Cape Town, Western Cape 7570, South Africa
  • CHUS - Hospital Clinico Universitario-Servicio de Oncologia ( Site 2404)
    Santiago de Compostela, La Coruna 15706, Spain
  • HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON-ONCOLOGY ( Site 2401)
    Madrid, Madrid, Comunidad de 28009, Spain
  • Hospital Universitari Vall d'Hebron-Oncology ( Site 2400)
    Barcelona, 08035, Spain
  • Hospital Universitario Juan Ramon Jimenez-Oncología Medica ( Site 2402)
    Huelva, 21005, Spain
  • National Taiwan University Cancer Center (NTUCC) ( Site 4205)
    Taipei City, Taipei 106, Taiwan
  • Changhua Christian Hospital ( Site 4203)
    Changhua, 50006, Taiwan
  • Kaohsiung Medical University Chung-Ho Memorial Hospital ( Site 4207)
    Kaohsiung City, 807, Taiwan
  • E-Da hospital ( Site 4208)
    Kaohsiung City, 82445, Taiwan
  • Chang Gung Memorial Hospital at Kaohsiung ( Site 4200)
    Kaohsiung City, 83301, Taiwan
  • National Cheng Kung University Hospital ( Site 4202)
    Tainan, 704, Taiwan
  • National Taiwan University Hospital-Oncology ( Site 4204)
    Taipei, 10002, Taiwan
  • Chulalongkorn University ( Site 4301)
    Bangkok, Bangkok 10330, Thailand

Showing the first 100 of 110 sites across 16 countries.

08

References and documents

Publications

  • Felip E, Rojas CI, Schenker M, Kowalski DM, Casarini IA, Csoszi T, Sendur MAN, Martins J, Calles Blanco A, Wang CC, Wang M, Ramirez Fallas RAL, Yoshioka H, Nair S, Song X, Deng X, Lala M, Eiras R, Takahashi T. Subcutaneous versus intravenous pembrolizumab, in combination with chemotherapy, for treatment of metastatic non-small-cell lung cancer: the phase III 3475A-D77 trial. Ann Oncol. 2025 Jul;36(7):775-785. doi: 10.1016/j.annonc.2025.03.012. Epub 2025 Mar 27. PubMed 40157574 ↗

Study documents

  • Protocol and statistical analysis plan · Feb 6, 2024

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

09

Registry details

Key details

Study ID
NCT05722015
Lead sponsor
Merck Sharp & Dohme LLC
Responsible party
Sponsor
First posted
Feb 10, 2023
Start date
Feb 14, 2023
Primary completion
Jul 12, 2024
Completion
May 22, 2028 (estimated)
Results posted
Jul 28, 2025
Last update
Aug 26, 2026

Study contacts

Medical Director
study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.

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