Clinical trial · Interventional
Study of Pemetrexed+Platinum Chemotherapy With or Without Pembrolizumab (MK-3475) in Participants With First Line Metastatic Nonsquamous Non-small Cell Lung Cancer (MK-3475-189/KEYNOTE-189)-Japan Extension Study
A Randomized, Double-Blind, Phase III Study of Platinum+Pemetrexed Chemotherapy With or Without Pembrolizumab (MK-3475) in First Line Metastatic Non-squamous Non-small Cell Lung Cancer Subjects (KEYNOTE-189)
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Non-Small-Cell Lung Carcinoma | Lung Non-Small Cell Carcinoma | ALIAS | 0.90 |
Interventions
Interventions (8)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Carboplatin | Drug | Carboplatin | ALIAS |
| Cisplatin | Drug | Cisplatin | ALIAS |
| Dexamethasone 4 mg | Drug | Dexamethasone | ALIAS |
| Folic acid 350-1000 μg | Dietary Supplement | — | UNRESOLVED |
| Pembrolizumab 200 mg | Biological | Pembrolizumab | ALIAS |
| Pemetrexed | Drug | Pemetrexed | ALIAS |
| Saline solution | Drug | — | UNRESOLVED |
| Vitamin B12 1000 μg | Dietary Supplement | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Pembrolizumab with Pemetrexed and Platinum Chemotherapy Followed by Pembrolizumab and Pemetrexed
- description
- Participants receive pembrolizumab 200 mg intravenously (IV) PLUS pemetrexed 500 mg/m\^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m\^2 IV OR carboplatin Area Under the Curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by pembrolizumab 200 mg IV PLUS pemetrexed 500 mg/m\^2 IV Q3W until progression. Participants who receive pembrolizumab 200 mg IV Q3W for up to 2 years, but experience disease progression, are eligible to receive a second course of pembrolizumab monotherapy 200 mg IV Q3W, at the investigator's discretion, for up to another year.
- interventionNames
- Biological: Pembrolizumab 200 mg
- Drug: Cisplatin
- Drug: Carboplatin
- Drug: Pemetrexed
- Dietary Supplement: Folic acid 350-1000 μg
- Dietary Supplement: Vitamin B12 1000 μg
- Drug: Dexamethasone 4 mg
- type
- ACTIVE_COMPARATOR
- label
- Placebo with Pemetrexed and Platinum Chemotherapy Followed by Placebo and Pemetrexed
- description
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Has a histologically-confirmed or cytologically confirmed diagnosis of stage IV nonsquamous NSCLC. * Has confirmation that epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK)-directed therapy is not indicated. * Has measurable disease. * Has not received prior systemic treatment for their advanced/metastatic NSCLC. * Can provide tumor tissue. * Has a life expectancy of at least 3 months. * Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status. * Has adequate organ function * If female of childbearing potential, is willing to use adequate contraception for the course of the study through 120 days after the last dose of study medication or through 180 days after last dose of chemotherapeutic agents. * If male with a female partner(s) of child-bearing potential, must agree to use adequate contraception starting with the first dose of study medication through 120 days after the last dose of study medication or through 180 days after last dose of chemotherapeutic agents. Exclusion Criteria: * Has predominantly squamous cell histology NSCLC. * Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to administration of pembrolizumab. * Before the first dose of study medication: a) Has received prior systemic cytotoxic chemotherapy for metastatic disease, b) Has received antineoplastic biological therapy (e.g. erlotinib, crizotinib, cetuximab), c) Had major surgery (\<3 weeks prior to first dose) * Received radiation therapy to the lung that is \>30 Gray (Gy) within 6 months of the first dose of study medication. * Completed palliative radiotherapy within 7 days of the first dose of study medication. * Is expected to require any other form of antineoplastic therapy while on study. * Received a live-virus vaccination within 30 days of planned start of study medication. * Has clinically active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, peritoneal carcinomatosis. * Known history of prior malignancy except if participant has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy, except for successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers. * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. * Previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb). * Known sensitivity to any component of cisplatin, carboplatin or pemetrexed. * Has active autoimmune disease that has required systemic treatment in past 2 years. * Is on chronic systemic steroids. * Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), other than an aspirin dose ≤1.3 g per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam). * Is unable or unwilling to take folic acid or vitamin B12 supplementation. * Had prior treatment with any other anti-programmed cell death-1 (PD-1), or PD-ligand 1 (PD-L1) or PD-L2 agent or an antibody targeting other immuno-regulatory receptors or mechanisms. Has participated in any other pembrolizumab study and has been treated with pembrolizumab. * Has an active infection requiring therapy. * Has known history of Human Immunodeficiency Virus (HIV). * Has known active Hepatitis B or C. * Has known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial. * Is a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol). * Has symptomatic ascites or pleural effusion. * Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis. * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.
References
Publications (4)
- RESULTHorinouchi H, Nogami N, Saka H, Nishio M, Tokito T, Takahashi T, Kasahara K, Hattori Y, Ichihara E, Adachi N, Noguchi K, Souza F, Kurata T. Pembrolizumab plus pemetrexed-platinum for metastatic nonsquamous non-small-cell lung cancer: KEYNOTE-189 Japan Study. Cancer Sci. 2021 Aug;112(8):3255-3265. doi: 10.1111/cas.14980. Epub 2021 Jun 15. PMID 34036692
- DERIVEDGadgeel SM, Rodriguez-Abreu D, Halmos B, Garassino MC, Kurata T, Cheng Y, Jensen E, Shamoun M, Rajagopalan K, Paz-Ares L. Pembrolizumab Plus Chemotherapy for Metastatic NSCLC With Programmed Cell Death Ligand 1 Tumor Proportion Score Less Than 1%: Pooled Analysis of Outcomes After Five Years of Follow-Up. J Thorac Oncol. 2024 Aug;19(8):1228-1241. doi: 10.1016/j.jtho.2024.04.011. Epub 2024 Apr 18. PMID 38642841
- DERIVEDCheng Y, Yang JC, Okamoto I, Zhang L, Hu J, Wang D, Hu C, Zhou J, Wu L, Cao L, Liu J, Zhang H, Sun H, Wang Z, Gao H, Yan Y, Xiao S, Lin J, Pietanza MC, Kurata T. Pembrolizumab plus chemotherapy for advanced non-small-cell lung cancer without tumor PD-L1 expression in Asia. Immunotherapy. 2023 Sep;15(13):1029-1044. doi: 10.2217/imt-2023-0043. Epub 2023 Jul 19. PMID 37465924
- DERIVEDRolfo C, Hess LM, Jen MH, Peterson P, Li X, Liu H, Lai Y, Sugihara T, Kiiskinen U, Vickers A, Summers Y. External control cohorts for the single-arm LIBRETTO-001 trial of selpercatinib in RET+ non-small-cell lung cancer. ESMO Open. 2022 Aug;7(4):100551. doi: 10.1016/j.esmoop.2022.100551. Epub 2022 Aug 2. PMID 35930972