NCT05722015 · CITED IN SOURCE DOCUMENTS

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)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-08-26

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · NOT POSTED

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

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outcome · NOT POSTED

Objective Response Rate (ORR)

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outcome · NOT POSTED

Progression-free Survival (PFS)

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outcome · NOT POSTED

Overall Survival (OS)

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outcome · NOT POSTED

Duration of Response (DOR)

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outcome · NOT POSTED

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

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outcome · NOT POSTED

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

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outcome · NOT POSTED

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

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outcome · NOT POSTED

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

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outcome · NOT POSTED

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

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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.
intervention Names
Biological: Pembrolizumab Formulated with Berahyaluronidase Alfa
Drug: Pemetrexed
Drug: Cisplatin
Drug: Carboplatin
Drug: Paclitaxel
Drug: Nab-paclitaxel
Drug: Filgrastim
Drug: Pegylated filgrastim
label
Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy
type
EXPERIMENTAL
description
Participants with treatment-naïve metastatic NSCLC receive 400 mg pembrolizumab intravenous (IV) infusion in combination with platinum doublet chemotherapy.
intervention Names
Drug: Pemetrexed
Drug: Cisplatin
Drug: Carboplatin
Drug: Paclitaxel
Drug: Nab-paclitaxel
Biological: Pembrolizumab
Drug: Filgrastim
Drug: Pegylated filgrastim
label
Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy
description
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.
name
Pembrolizumab Formulated with Berahyaluronidase Alfa
other Names
MK-3475A
type
BIOLOGICAL
arm Group Labels
Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy
Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy
description
Pemetrexed 500 mg/m² by IV Infusion will be administered for nonsquamous NSCLC as per the schedule specified in arm.
name
Pemetrexed
other Names
Alimta
type
DRUG
arm Group Labels
Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy
Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy
description
Cisplatin 75 mg/m² by IV Infusion will be administered for nonsquamous and squamous NSCLC as per the schedule specified in arm.
name
Cisplatin
other Names
Platinol-AQ
type
DRUG
arm Group Labels
Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy
Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy
description
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.
name
Carboplatin
type
DRUG
arm Group Labels
Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy
Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy
description
Paclitaxel 200 mg/m² by IV Infusion will be administered for squamous NSCLC as per the schedule specified in arm.
name
Paclitaxel
other Names
Taxol
type
DRUG
arm Group Labels
Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy
Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy
description
Nab-paclitaxel 100 mg/m² by IV Infusion will be administered for squamous NSCLC as per the schedule specified in arm.
name
Nab-paclitaxel
other Names
Albumin-bound paclitaxel
type
DRUG
arm Group Labels
Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy
description
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.
name
Pembrolizumab
other Names
MK-3475, KEYTRUDA
type
BIOLOGICAL
arm Group Labels
Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy
Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy
description
Filgrastim will be administered as per the schedule specified for the arm.
name
Filgrastim
type
DRUG
arm Group Labels
Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy
Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy
description
Pegylated filgrastim will be administered as per the schedule specified for the arm.
name
Pegylated filgrastim
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 377
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
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)
description
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.
measure
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)

secondary Outcomes

description
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.
measure
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)
description
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.
measure
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)
description
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.
measure
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)
description
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.
measure
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)
description
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.
measure
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.
description
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.
measure
Objective Response Rate (ORR)
time Frame
Up to approximately 28 months
description
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.
measure
Progression-free Survival (PFS)
time Frame
Up to approximately 28 months
description
OS was defined as the time from randomization to death due to any cause.
measure
Overall Survival (OS)
time Frame
Up to approximately 28 months
description
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.
measure
Duration of Response (DOR)
time Frame
Up to approximately 28 months
description
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 .
measure
Number of Participants Who Experienced at Least One Adverse Event (AE)
time Frame
Up to approximately 28 months
description
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.
measure
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
time Frame
Up to approximately 28 months
description
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.
measure
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

Full study description

brief 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.
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.

Source references

references

citation
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.
pmid
40157574
type
RESULT