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
- Conditions
- Metastatic Non-small Cell Lung Cancer
- Interventions
- Registration Number
- NCT06212752
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 39
- 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
- Has not adequately recovered from major surgery or has ongoing surgical complications
- Has a history of allogenic tissue/solid organ transplant
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy Pembrolizumab (+) Berahyaluronidase alfa 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. Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy Pemetrexed 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. Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy Cisplatin 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. Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy Carboplatin 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. Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy Paclitaxel 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. Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy Nab-paclitaxel 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. Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy Filgrastim 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. Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy Pegylated filgrastim 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. Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy Pemetrexed 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. Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy Cisplatin 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. Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy Carboplatin 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. Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy Paclitaxel 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. Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy Nab-paclitaxel 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. Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy Pembrolizumab 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. Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy Filgrastim 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. Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy Pegylated filgrastim 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.
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) Up to ~ 16 months 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.
- Secondary Outcome Measures
Name Time Method 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) 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 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) 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 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) 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: Trough Serum Concentration (Ctrough) of Pembrolizumab After the First Dose At designated time points (Up to ~28 months) 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.
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) 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.
Cycle 3: Maximum Serum Concentration (Cmax) 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) 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.
Number of Participants Who Test Positive for Anti-Drug Antibodies (ADAs) for Pembrolizumab At designated time points (Up to ~28 months) 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.
Progression-free Survival (PFS) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) Up to ~59 months 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.
Overall Survival (OS) Up to ~59 months OS is defined as the time from randomization to death due to any cause.
Duration of Response (DOR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) Up to ~59 months 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.
Number of Participants Who Experienced at Least One Adverse Event (AE) Up to~28 months 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.
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) Up to~25 months 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.
Trial Locations
- 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
Scroll for more (8 remaining)Fujita Health University ( Site 4406)🇯🇵Toyoake, Aichi-ken, Japan