AzTrials
AzTrials

Metastatic Non-small Cell Lung CancerPhase 3NCT06212752

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 study testing Pembrolizumab Formulated with Berahyaluronidase Alfa, Pemetrexed and Cisplatin in people with Metastatic Non-small Cell Lung Cancer, run by Merck Sharp & Dohme LLC at 18 sites in Japan.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Non-small Cell Lung Cancer
What is being tested?
Pembrolizumab Formulated with Berahyaluronidase Alfa, Pemetrexed and Cisplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
18 sitesJapan
Study dates
13 Jun 2023to 22 May 2028
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 14Show fewer
  • 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

Trial locations and contacts

18 sites in 1 country.

18 sites in 1 country

Japan18 sites

  • Juntendo University Hospital ( Site 4413)

    Bunkyo-ku, Tokyo, 1138431

  • National Hospital Organization Kyushu Medical Center ( Site 4411)

    Fukuoka, 810-8563

  • National Hospital Organization Kyushu Cancer Center ( Site 4410)

    Fukuoka, 811-1395

  • Kansai Medical University Hospital ( Site 4408)

    Hirakata, Osaka, 573-1191

  • Saitama Prefectural Cancer Center ( Site 4402)

    Ina-machi, Saitama, 362-0806

  • Kurashiki Central Hospital ( Site 4409)

    Kurashiki, Okayama-ken, 710-8602

  • Kurume University Hospital ( Site 4412)

    Kurume, Fukuoka, 830-0011

  • Shizuoka Cancer Center ( Site 4405)

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

  • Miyagi Cancer Center ( Site 4401)

    Natori-shi, Miyagi, 981-1293

  • Osaka International Cancer Institute ( Site 4407)

    Osaka, 541-8567

  • Gunma Prefectural Cancer Center ( Site 4416)

    Otashi, Gunma, 373-8550

  • National Hospital Organization Hokkaido Cancer Center ( Site 4415)

    Sapporo, Hokkaido, 003-0804

  • Sendai Kousei Hospital ( Site 4400)

    Sendai, Miyagi, 9800873

  • Osaka Medical and Pharmaceutical University Hospital ( Site 4414)

    Takatsuki, Osaka, 569-8686

  • Nippon Medical School Hospital ( Site 4403)

    Tokyo, 113-8603

  • Fujita Health University ( Site 4406)

    Toyoake, Aichi-ken, 470-1192

  • Tochigi Cancer Center ( Site 4417)

    Utsunomiya, Tochigi, 320-0834

  • Kanagawa Cardiovascular and Respiratory Center ( Site 4404)

    Yokohama, Kanagawa, 236-0051

Other trials in Japan

About this study

Official title: A Phase 3 Randomized, Open-label Clinical Study to Evaluate the Pharmacokinetics and Safety of Subcutaneous Pembrolizumab Coformulated With Hyaluronidase (MK-3475A) Versus Intravenous Pembrolizumab, Administered With Chemotherapy, in the First-line Treatment of Participants With Metastatic Non-small Cell Lung Cancer

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.

Read the 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.

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.

Being tested
Pembrolizumab Formulated with Berahyaluronidase Alfa, Pemetrexed, Cisplatin, Carboplatin, Paclitaxel
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Pembrolizumab Formulated with Berahyaluronidase AlfaBiological

    Also called MK-3475A

    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.

  • PemetrexedDrug

    Also called Alimta

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

  • CisplatinDrug

    Also called Platinol-AQ

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

  • CarboplatinDrug

    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.

  • PaclitaxelDrug

    Also called Taxol

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

  • Nab-paclitaxelDrug

    Also called Albumin-bound paclitaxel

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

  • PembrolizumabBiological

    Also called MK-3475, KEYTRUDA

    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.

  • FilgrastimDrug

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

  • Pegylated filgrastimDrug

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

Study groups in NCT06212752
Study groupRoleWhat they receive
Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet ChemotherapyExperimentalJapanese 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.
Receives: Biological: Pembrolizumab Formulated with Berahyaluronidase Alfa; Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin; Drug: Paclitaxel; Drug: Nab-paclitaxel; Drug: Filgrastim; Drug: Pegylated filgrastim
Arm 2: Pembrolizumab + Platinum Doublet ChemotherapyActive comparatorJapanese 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.
Receives: Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin; Drug: Paclitaxel; Drug: Nab-paclitaxel; Biological: Pembrolizumab; Drug: Filgrastim; Drug: Pegylated filgrastim

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to ~ 16 months

Secondary outcomes (12)

  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.

    Measured: 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)

  2. 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.

    Measured: 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)

  3. 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.

    Measured: 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)

  4. 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.

    Measured: At designated time points (Up to ~28 months)

  5. 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.

    Measured: At designated time points (Up to ~28 months)

  6. 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.

    Measured: 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)

  7. 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.

    Measured: At designated time points (Up to ~28 months)

  8. 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.

    Measured: Up to ~59 months

  9. Overall Survival (OS)

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

    Measured: Up to ~59 months

  10. 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.

    Measured: Up to ~59 months

  11. 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.

    Measured: Up to~28 months

  12. 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.

    Measured: Up to~25 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Jan 2024
  2. Study start13 Jun 2023
  3. Primary completion6 Nov 2024
  4. Study completion22 May 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06212752
Sponsor's protocol ID
3475A-D77 Japan Extension
Other IDs
MK-3475A-D77, 2022-501506-36-00, jRCT2031230049, U1111-1280-9384
Status last verified
Jul 2026
First submitted
9 Jan 2024
Last updated
26 Aug 2026
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pembrolizumab Formulated with Berahyaluronidase Alfa, Pemetrexed and Cisplatin in people with Metastatic Non-small Cell Lung Cancer, run by Merck Sharp & Dohme LLC at 18 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 26 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Nov 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) (time frame: Up to ~ 16 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06212752.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in