This is a Japan Extension Study of Global Study MK-3475-189 (NCT02578680). This is an efficacy and safety study of pembrolizumab (MK-3475) combined with pemetrexed/platinum chemotherapy versus pemetrexed/platinum chemotherapy alone in adult Japanese participants with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) who have not previously received systemic therapy for advanced disease. Participants will be randomly assigned to receive pembrolizumab combined with pemetrexed/platinum (Investigators choice of cisplatin or carboplatin), OR pemetrexed/platinum (Investigators choice of cisplatin or carboplatin). With Amendment 11 (effective date 31-Jan-2022), once the study objectives have been met or the study has ended, participants will be discontinued from this study and will be enrolled in an extension study to continue protocol-defined assessments and treatment. The primary hypothesis is that pembrolizumab in combination with pemetrexed/platinum chemotherapy prolongs Progression-Free Survival (PFS) and Overall Survival (OS) compared to pemetrexed/platinum chemotherapy alone.
The MK-3475-189-Japan Extension Study will be identical to the global study (e.g. inclusion and exclusion criteria, study primary and secondary outcome measures and study procedures). The MK-3475-189-Japanese Extension Study enrolled a total of 30 participants and the analyses included 10 participants (pembrolizumab =4; control = 6) that had been previously enrolled in the MK-3475-189 global study (NCT02578680), resulting in a total of 40 participants.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
40
IV infusion
IV infusion
IV infusion
IV infusion
Orally; at least 5 doses of folic acid must be taken during the 7 days preceding the first dose of pemetrexed, and folic acid dosing must continue during the full course of therapy and for 21 days after the last dose of pemetrexed.
Intramuscular injection in the week preceding the first dose of pemetrexed and once every 3 cycles thereafter. Subsequent vitamin B12 injections may be given the same day as pemetrexed administration.
For prophylaxis; orally twice per day (or equivalent). Taken the day before, day of, and day after pemetrexed administration.
IV infusion
National Hospital Organization Nagoya Medical Center ( Site 0324)
Nagoya, Aichi-ken, Japan
Kurume University Hospital ( Site 0326)
Kurume, Fukuoka, Japan
Hyogo Cancer Center ( Site 0325)
Akashi, Hyōgo, Japan
Kanazawa University Hospital ( Site 0328)
Kanazawa, Ishikawa-ken, Japan
Kansai Medical University Hospital ( Site 0313)
Hirakata, Osaka, Japan
Shizuoka Cancer Center Hospital and Research Institute ( Site 0322)
Sunto-gun, Shizuoka, Japan
National Hospital Organization Shikoku Cancer Center ( Site 0303)
Matsuyama, Japan
Okayama University Hospital ( Site 0327)
Okayama, Japan
National Cancer Center Hospital ( Site 0301)
Tokyo, Japan
The Cancer Institute Hospital of JFCR ( Site 0323)
Tokyo, Japan
Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Central Imaging
PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 is presented.
Time frame: Up to approximately 31 months
Overall Survival (OS)
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. The OS is presented.
Time frame: Up to approximately 31 months
Overall Response Rate (ORR) Per RECIST 1.1 as Assessed by Blinded Central Imaging
ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The percentage of participants who experienced a CR or PR is presented.
Time frame: Up to approximately 31 months
Duration of Response (DOR) Per RECIST 1.1 as Assessed by Blinded Central Imaging
For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of a CR or PR until PD or death. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. DOR assessments were based on blinded central imaging review with confirmation. The DOR per RECIST 1.1 for all participants who experienced a confirmed CR or PR is presented.
Time frame: Up to approximately 31 months
Number of Participants Who Experienced an Adverse Event (AE)
An adverse event was defined as any untoward medical occurrence in a clinical study participant administered a pharmaceutical product which did not necessarily have a causal relationship with this treatment. An adverse event was any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that was temporally associated with the use of the study drug was also an adverse event. Per protocol, final analysis for this outcome measure was performed for the first course of pembrolizumab or placebo treatment. The number of participants who experienced an AE is reported.
Time frame: Up to approximately 24 months
Number of Participants Who Discontinued Any Study Drug Due to an AE
An adverse event was defined as any untoward medical occurrence in a clinical study participant administered a pharmaceutical product which did not necessarily have a causal relationship with this treatment. An adverse event was any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that was temporally associated with the use of the study drug was also an adverse event. Per protocol, final analysis for this outcome measure was performed for the first course of pembrolizumab or placebo treatment. The number of participants who discontinued study treatment due to an AE is presented.
Time frame: Up to approximately 21 months
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