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

Phase 3Active Not RecruitingNCT06212752

Merck Sharp & Dohme LLC39 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Metastatic Non-small Cell Lung Cancer

Interventions

Pembrolizumab Formulated with Berahyaluronidase AlfaBIOLOGICAL

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

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

CisplatinDRUG

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

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

Nab-paclitaxelDRUG

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

PembrolizumabBIOLOGICAL

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (18)

Fujita Health University ( Site 4406)

Toyoake, Aichi-ken, Japan

Kurume University Hospital ( Site 4412)

Kurume, Fukuoka, Japan

Gunma Prefectural Cancer Center ( Site 4416)

Otashi, Gunma, Japan

National Hospital Organization Hokkaido Cancer Center ( Site 4415)

Sapporo, Hokkaido, Japan

Kanagawa Cardiovascular and Respiratory Center ( Site 4404)

Yokohama, Kanagawa, Japan

Miyagi Cancer Center ( Site 4401)

Natori-shi, Miyagi, Japan

Sendai Kousei Hospital ( Site 4400)

Sendai, Miyagi, Japan

Kurashiki Central Hospital ( Site 4409)

Kurashiki, Okayama-ken, Japan

Kansai Medical University Hospital ( Site 4408)

Hirakata, Osaka, Japan

Osaka Medical and Pharmaceutical University Hospital ( Site 4414)

Takatsuki, Osaka, Japan

...and 8 more locations

Outcomes

Primary Outcomes

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.

Time frame: Up to ~ 16 months

Secondary Outcomes

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, 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.

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)

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)

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: 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.

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

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)

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.

Time frame: 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.

Time frame: Up to ~59 months

Overall Survival (OS)

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

Time frame: 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.

Time frame: Up to ~59 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.

Time frame: Up to~28 months

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

Time frame: Up to~25 months