A Study of Subcutaneous (SC) Pembrolizumab Coformulated With Hyaluronidase (MK-3475A) vs Intravenous Pembrolizumab in Adult Participants With Metastatic Non-small Cell Lung Cancer (NSCLC) (MK-3475A-D77)-Japan Extension
- Registration Number
- NCT06212752
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
This study is to assess the pharmacokinetics (PK) and safety of SC MK-3475A 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 MK-3475A subcutaneous (SC) is noninferior to pembrolizumab IV with respect to ...
- 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.
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Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 378
- 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 2 (Pembrolizumab + Platinum Doublet Chemotherapy) Paclitaxel Participants with treatment-naïve metastatic NSCLC will receive Pembrolizumab IV in combination with platinum doublet chemotherapy. Arm 2 (Pembrolizumab + Platinum Doublet Chemotherapy) Nab-paclitaxel Participants with treatment-naïve metastatic NSCLC will receive Pembrolizumab IV in combination with platinum doublet chemotherapy. Arm 2 (Pembrolizumab + Platinum Doublet Chemotherapy) Filgrastim Participants with treatment-naïve metastatic NSCLC will receive Pembrolizumab IV in combination with platinum doublet chemotherapy. Arm 1 (MK-3475A + Platinum Doublet Chemotherapy) Filgrastim Participants with treatment-naïve metastatic NSCLC will receive MK 3475A SC in combination with platinum doublet chemotherapy. Arm 2 (Pembrolizumab + Platinum Doublet Chemotherapy) Pegylated filgrastim Participants with treatment-naïve metastatic NSCLC will receive Pembrolizumab IV in combination with platinum doublet chemotherapy. Arm 1 (MK-3475A + Platinum Doublet Chemotherapy) Pegylated filgrastim Participants with treatment-naïve metastatic NSCLC will receive MK 3475A SC in combination with platinum doublet chemotherapy. Arm 2 (Pembrolizumab + Platinum Doublet Chemotherapy) Pemetrexed Participants with treatment-naïve metastatic NSCLC will receive Pembrolizumab IV in combination with platinum doublet chemotherapy. Arm 2 (Pembrolizumab + Platinum Doublet Chemotherapy) Cisplatin Participants with treatment-naïve metastatic NSCLC will receive Pembrolizumab IV in combination with platinum doublet chemotherapy. Arm 1 (MK-3475A + Platinum Doublet Chemotherapy) Pembrolizumab coformulated with hyaluronidase Participants with treatment-naïve metastatic NSCLC will receive MK 3475A SC in combination with platinum doublet chemotherapy. Arm 2 (Pembrolizumab + Platinum Doublet Chemotherapy) Carboplatin Participants with treatment-naïve metastatic NSCLC will receive Pembrolizumab IV in combination with platinum doublet chemotherapy. Arm 1 (MK-3475A + Platinum Doublet Chemotherapy) Cisplatin Participants with treatment-naïve metastatic NSCLC will receive MK 3475A SC in combination with platinum doublet chemotherapy. Arm 1 (MK-3475A + Platinum Doublet Chemotherapy) Paclitaxel Participants with treatment-naïve metastatic NSCLC will receive MK 3475A SC in combination with platinum doublet chemotherapy. Arm 1 (MK-3475A + Platinum Doublet Chemotherapy) Nab-paclitaxel Participants with treatment-naïve metastatic NSCLC will receive MK 3475A SC in combination with platinum doublet chemotherapy. Arm 2 (Pembrolizumab + Platinum Doublet Chemotherapy) Pembrolizumab Participants with treatment-naïve metastatic NSCLC will receive Pembrolizumab IV in combination with platinum doublet chemotherapy. Arm 1 (MK-3475A + Platinum Doublet Chemotherapy) Pemetrexed Participants with treatment-naïve metastatic NSCLC will receive MK 3475A SC in combination with platinum doublet chemotherapy. Arm 1 (MK-3475A + Platinum Doublet Chemotherapy) Carboplatin Participants with treatment-naïve metastatic NSCLC will receive MK 3475A SC in combination with platinum doublet chemotherapy.
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) Up to ~72 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 RECIST 1.1 as assessed by BICR.
- Secondary Outcome Measures
Name Time Method Area Under the Curve (AUC) of Pembrolizumab Measured After the First Dose At designated time points (Up to ~14 months) AUC is defined as area under curve exposure. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine AUC.
Trough Concentration (Ctrough) of Pembrolizumab Measured at Steady State At designated time points (Up to ~18 months) 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.
Maximum Serum Concentration (Cmax) of Pembrolizumab Measured After the First Dose At designated time points (Up to ~28 months) Cmax is defined as the peak concentration over the dosing interval. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmax.
Trough Concentration (Ctrough) of Pembrolizumab Measured After the First Dose At designated time points (Up to ~28 months) Ctrough is defined as the trough concentration. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Ctrough.
Area Under the Curve (AUC) of Pembrolizumab Measured at Steady State At designated time points (Up to ~28 months) AUC is defined as area under curve exposure at steady state. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine AUC.
Maximum Serum Concentration (Cmax) of Pembrolizumab Measured at Steady State At designated time points (Up to ~28 months) Cmax is defined as the peak concentration over the dosing interval in steady-state. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmax
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 ~72 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 ~72 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 ~72 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.
Change From Baseline in the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) Global Health Status/Quality of Life (GHS/QoL) Score-Items 29 and 30 Baseline and up to ~28 months EORTC QLQ-C30 is a psychometrically and clinically validated instrument appropriate for assessing HRQoL in oncology studies. The EORTC QLQ-C30 is the most widely used cancer-specific HRQoL instrument, which contains 30 items and measures 5 functional dimensions (physical, role, emotional, cognitive and social), 3 symptom items (fatigue, nausea/vomiting, and ...
Change From Baseline in the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) Physical Functioning Score-Items 1 to 5 Baseline and up to ~28 months The EQ-5D-5L is a standardized instrument for use as a measure of health outcome and will provide data to develop health utilities for use in health economic analyses. The 5 health state dimensions in the EQ-5D-5L include the following: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension is rated on a 5-point scale ...
Change From Baseline in the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) Role Functioning Score-Items 6 and 7 Baseline and up to ~28 months The EQ-5D-5L is a standardized instrument for use as a measure of health outcome and will provide data to develop health utilities for use in health economic analyses. The 5 health state dimensions in the EQ-5D-5L include the following: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension is rated on a 5-point scale ...
Trial Locations
- Locations (18)
Miyagi Cancer Center ( Site 4401)
🇯🇵Natori, Miyagi, Japan
Fujita Health University ( Site 4406)
🇯🇵Toyoake, Aichi, Japan
Kurume University Hospital ( Site 4412)
🇯🇵Kurume, Fukuoka, Japan
Gunma Prefectural Cancer Center ( Site 4416)
🇯🇵Otashi, Gunma, Japan
Kanagawa Cardiovascular and Respiratory Center ( Site 4404)
🇯🇵Yokohama, Kanagawa, Japan
Sendai Kousei Hospital ( Site 4400)
🇯🇵Sendai, Miyagi, Japan
Kansai Medical University Hospital ( Site 4408)
🇯🇵Hirakata, Osaka, Japan
Kurashiki Central Hospital ( Site 4409)
🇯🇵Kurashiki, Okayama, Japan
Osaka Medical and Pharmaceutical University Hospital ( Site 4414)
🇯🇵Takatsuki, Osaka, Japan
Saitama Prefectural Cancer Center ( Site 4402)
🇯🇵Ina-machi, Saitama, Japan
Shizuoka Cancer Center ( Site 4405)
🇯🇵Nagaizumi-cho,Sunto-gun, Shizuoka, Japan
National Hospital Organization Kyushu Medical Center ( Site 4411)
🇯🇵Fukuoka, Japan
National Hospital Organization Kyushu Cancer Center ( Site 4410)
🇯🇵Fukuoka, Japan
Juntendo University Hospital ( Site 4413)
🇯🇵Bunkyo-ku, Tokyo, Japan
Tochigi Cancer Center ( Site 4417)
🇯🇵Utsunomiya, Tochigi, Japan
Osaka International Cancer Institute ( Site 4407)
🇯🇵Osaka, Japan
Nippon Medical School Hospital ( Site 4403)
🇯🇵Tokyo, Japan
National Hospital Organization Hokkaido Cancer Center ( Site 4415)
🇯🇵Sapporo, Hokkaido, Japan