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

NCT06212752 | Active Not Recruiting Phase 3 Results DMC

• 4 other identifiers: 3475A-D77 Japan ExtensionMK-3475A-D772022-501506-36-00jRCT2031230049
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 18

Brief Summary

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.

Conditions

Metastatic Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (12)

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

  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

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

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

  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

  At designated time points (Up to ~28 months)

Study Arms (2)

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

EXPERIMENTAL

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.

Biological: Pembrolizumab (+) Berahyaluronidase alfa; Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin; Drug: Paclitaxel; Drug: Nab-paclitaxel; Drug: Filgrastim; Drug: Pegylated filgrastim

Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy

ACTIVE COMPARATOR

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

Interventions

Pembrolizumab (+) Berahyaluronidase alfa BIOLOGICAL

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.

Also known as: MK-3475A

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

Pemetrexed DRUG

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

Also known as: Alimta

Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy; Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy

Cisplatin DRUG

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

Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy; Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy

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.

Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy; Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy

Paclitaxel DRUG

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

Also known as: Taxol

Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy; Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy

Nab-paclitaxel DRUG

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

Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy; Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy

Pembrolizumab BIOLOGICAL

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.

Also known as: MK-3475, KEYTRUDA

Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy

Filgrastim DRUG

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

Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy; Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy

Pegylated filgrastim DRUG

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

Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy; Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (18)

Fujita Health University ( Site 4406)

Toyoake, Aichi-ken, 470-1192, Japan

Location

Kurume University Hospital ( Site 4412)

Kurume, Fukuoka, 830-0011, Japan

Location

Gunma Prefectural Cancer Center ( Site 4416)

Otashi, Gunma, 373-8550, Japan

Location

National Hospital Organization Hokkaido Cancer Center ( Site 4415)

Sapporo, Hokkaido, 003-0804, Japan

Location

Kanagawa Cardiovascular and Respiratory Center ( Site 4404)

Yokohama, Kanagawa, 236-0051, Japan

Location

Miyagi Cancer Center ( Site 4401)

Natori-shi, Miyagi, 981-1293, Japan

Location

Sendai Kousei Hospital ( Site 4400)

Sendai, Miyagi, 9800873, Japan

Location

Kurashiki Central Hospital ( Site 4409)

Kurashiki, Okayama-ken, 710-8602, Japan

Location

Kansai Medical University Hospital ( Site 4408)

Hirakata, Osaka, 573-1191, Japan

Location

Osaka Medical and Pharmaceutical University Hospital ( Site 4414)

Takatsuki, Osaka, 569-8686, Japan

Location

Saitama Prefectural Cancer Center ( Site 4402)

Ina-machi, Saitama, 362-0806, Japan

Location

Shizuoka Cancer Center ( Site 4405)

Nagaizumi-cho,Sunto-gun, Shizuoka, 411-8777, Japan

Location

Tochigi Cancer Center ( Site 4417)

Utsunomiya, Tochigi, 320-0834, Japan

Location

Juntendo University Hospital ( Site 4413)

Bunkyo-ku, Tokyo, 1138431, Japan

Location

National Hospital Organization Kyushu Medical Center ( Site 4411)

Fukuoka, 810-8563, Japan

Location

National Hospital Organization Kyushu Cancer Center ( Site 4410)

Fukuoka, 811-1395, Japan

Location

Osaka International Cancer Institute ( Site 4407)

Osaka, 541-8567, Japan

Location

Nippon Medical School Hospital ( Site 4403)

Tokyo, 113-8603, Japan

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab; Pemetrexed; Cisplatin; Carboplatin; Paclitaxel; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Filgrastim

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Albumins; Proteins; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2024
• First Posted: January 19, 2024
• Study Start: June 13, 2023
• Primary Completion: November 6, 2024
• Study Completion (Estimated): May 22, 2028
• Last Updated: November 12, 2025
• Results First Posted: November 12, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

JP (18)