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Phase 3 Completed N=40 Randomized Triple-blind Treatment

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

Source: ClinicalTrials.gov NCT03950674 ↗
Enrolled (actual)
40
Serious AEs
35.6%
Results posted
Jun 2020
Primary outcomePrimary: Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Central Imaging — 16.5; 7.1 Months — p=0.12511
◆ Published Evidence
Established
57citations · ~11 / year
Pembrolizumab plus pemetrexed-platinum for metastatic nonsquamous non-small-cell lung cancer: KEYNOTE-189 Japan Study.
Cancer science · 2021 · Open access · High-confidence link

Summary

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.

Linked Publications (4)

  • Pembrolizumab plus pemetrexed-platinum for metastatic nonsquamous non-small-cell lung cancer: KEYNOTE-189 Japan Study.
    Cancer science · 2021 · 57 citations · Open access · High-confidence link
  • 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.
    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2024 · 36 citations · Open access · Likely link
  • External control cohorts for the single-arm LIBRETTO-001 trial of selpercatinib in RET+ non-small-cell lung cancer.
    ESMO open · 2022 · 17 citations · Open access · Likely link
  • Pembrolizumab plus chemotherapy for advanced non-small-cell lung cancer without tumor PD-L1 expression in Asia.
    Immunotherapy · 2023 · 10 citations · Open access · Likely link

Outcome Measures

OutcomeResultp-value
PRIMARY
Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Central Imaging
16.5; 7.1 0.12511
PRIMARY
Overall Survival (OS)
NA; 25.9 0.03127 sig
SECONDARY
Overall Response Rate (ORR) Per RECIST 1.1 as Assessed by Blinded Central Imaging
56.0; 33.3
SECONDARY
Duration of Response (DOR) Per RECIST 1.1 as Assessed by Blinded Central Imaging
13.6; 9.7
SECONDARY
Number of Participants Who Experienced an Adverse Event (AE)
25; 15
SECONDARY
Number of Participants Who Discontinued Any Study Drug Due to an AE
9; 3

Eligibility Criteria

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 ( 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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03950674) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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