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)-Japan Extension

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin; Drug: Paclitaxel; Drug: Nab-paclitaxel; Biological: Pembrolizumab; Drug: Filgrastim; Drug: Pegylated filgrastim; Biological: Pembrolizumab (+) Berahyaluronidase alfa

Detailed Description

Japan extension study will require approximately six years which includes one additional year (beyond the global study's last participant last study related contact) from the time the first participant (or their legally acceptable representative) provides informed consent until the last participant's last study related contact to complete.

The Japan extension study will include participants previously enrolled in Japan in the global study for MK-3475A-D77 (NCT05722015) plus the study will continue to enroll participants in Japan until the sample size for participants in Japan reaches approximately 39.

As of Amendment 1 of the supplemental statistical analysis plan (effective date: 23 Aug 2024), patient reported outcomes will no longer be the secondary outcome measures of the study.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 810-8563
    • National Hospital Organization Kyushu Medical Center ( Site 4411)
  • Fukuoka, Japan, 811-1395
    • National Hospital Organization Kyushu Cancer Center ( Site 4410)
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute ( Site 4407)
  • Tokyo, Japan, 113-8603
    • Nippon Medical School Hospital ( Site 4403)
  • Aichi-ken
    • Toyoake, Aichi-ken, Japan, 470-1192
      • Fujita Health University ( Site 4406)
  • Fukuoka
    • Kurume, Fukuoka, Japan, 830-0011
      • Kurume University Hospital ( Site 4412)
  • Gunma
    • Otashi, Gunma, Japan, 373-8550
      • Gunma Prefectural Cancer Center ( Site 4416)
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 003-0804
      • National Hospital Organization Hokkaido Cancer Center ( Site 4415)
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 236-0051
      • Kanagawa Cardiovascular and Respiratory Center ( Site 4404)
  • Miyagi
    • Natori-shi, Miyagi, Japan, 981-1293
      • Miyagi Cancer Center ( Site 4401)
    • Sendai, Miyagi, Japan, 9800873
      • Sendai Kousei Hospital ( Site 4400)
  • Okayama-ken
    • Kurashiki, Okayama-ken, Japan, 710-8602
      • Kurashiki Central Hospital ( Site 4409)
  • Osaka
    • Hirakata, Osaka, Japan, 573-1191
      • Kansai Medical University Hospital ( Site 4408)
    • Takatsuki, Osaka, Japan, 569-8686
      • Osaka Medical and Pharmaceutical University Hospital ( Site 4414)
  • Saitama
    • Ina-machi, Saitama, Japan, 362-0806
      • Saitama Prefectural Cancer Center ( Site 4402)
  • Shizuoka
    • Nagaizumi-cho,Sunto-gun, Shizuoka, Japan, 411-8777
      • Shizuoka Cancer Center ( Site 4405)
  • Tochigi
    • Utsunomiya, Tochigi, Japan, 320-0834
      • Tochigi Cancer Center ( Site 4417)
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 1138431
      • Juntendo University Hospital ( Site 4413)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy; Japanese 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 for18 cycles (up to approximately108 weeks) in combination with platinum doublet chemotherapy.	Drug: Pemetrexed; Pemetrexed 500 mg/m² by IV Infusion will be administered for nonsquamous NSCLC as per the schedule specified in arm.; Other Names: 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 Names: 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 Names: 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 Names: Albumin-bound paclitaxel; Drug: Filgrastim; Filgrastim will be administered as per the schedule specified for the arm.; Drug: Pegylated filgrastim; Pegylated filgrastim will be administered as per the schedule specified for the arm.; Biological: Pembrolizumab (+) Berahyaluronidase alfa; Pembrolizumab (+) Berahyaluronidase alfa SC will be administered for squamous and nonsquamous NSCLC as per the schedule specified in arm; participants may be eligible for second course.; Other Names: MK-3475A
Active Comparator: Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy; Japanese participants with treatment-naïve metastatic NSCLC receive 400 mg pembrolizumab intravenous (IV) infusion on Day 1 of each 6-week cycle for 18 cycles (up to approximately 108 weeks) in combination with platinum doublet chemotherapy.	Drug: Pemetrexed; Pemetrexed 500 mg/m² by IV Infusion will be administered for nonsquamous NSCLC as per the schedule specified in arm.; Other Names: 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 Names: 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 Names: 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 Names: 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 Names: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR was defined as the percentage of participants who have a confirmed 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, taking as reference the baseline sum diameters) per Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR). The percentage of participants with CR or PR were reported.	Up to ~ 16 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Test Positive for Anti-Drug Antibodies (ADAs) for Pembrolizumab	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.	At designated time points (Up to ~28 months)
Number of Participants Who Experienced at Least One 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 with an AE will be reported for Arms 1 and 2.	Up to~28 months
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.	Up to~25 months
Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to ~59 months
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.	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)
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.	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)
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.	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, Days4, 15, 29, and 42 postdose (cycle length = 42 days)
Cycle 3: Trough Serum Concentration (Ctrough) of Pembrolizumab at Steady State	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.	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)
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.	At designated time points (Up to ~28 months)
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.	At designated time points (Up to ~28 months)
Progression-free Survival (PFS) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)	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.	Up to ~59 months
Duration of Response (DOR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)	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.	Up to ~59 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2023
• Primary Completion (Actual): November 6, 2024
• Study Completion (Estimated): May 22, 2028

Study Registration Dates

• First Submitted: January 9, 2024
• First Submitted That Met QC Criteria: January 9, 2024
• First Posted (Actual): January 19, 2024

Study Record Updates

• Last Update Posted (Actual): November 12, 2025
• Last Update Submitted That Met QC Criteria: October 22, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Biological Factors; Carbohydrates; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Diterpenes; Intercellular Signaling Peptides and Proteins; Glycoproteins; Glycoconjugates; Platinum Compounds; Colony-Stimulating Factors; Hematopoietic Cell Growth Factors; Cytokines; Albumins; Granulocyte Colony-Stimulating Factor; Albumin-Bound Paclitaxel; Pemetrexed; Carboplatin; Paclitaxel; Cisplatin; pembrolizumab; 130-nm albumin-bound paclitaxel; Filgrastim
• Other Study ID Numbers: 3475A-D77 Japan Extension; 2022-501506-36-00 (Other Identifier: EU CT); MK-3475A-D77 (Other Identifier: MSD); jRCT2031230049 (Other Identifier: Japan Registry of Clinical Trials (jRCT))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No