Clinical Trials /

Study of Pembrolizumab Versus Docetaxel in Participants Previously Treated for Non-Small Cell Lung Cancer (MK-3475-033/KEYNOTE-033)

NCT02864394

Description:

The purpose of this study is to assess the efficacy of pembrolizumab (MK-3475) versus docetaxel in participants with non-small cell lung cancer (NSCLC) with programmed cell death ligand 1 (PD-L1) positive tumors who have experienced disease progression after platinum-containing systemic therapy. The primary hypotheses of this study are that pembrolizumab (MK-3475) prolongs overall survival (OS) and that pembrolizumab prolongs progression-free survival (PFS), compared to docetaxel in participants with PD-L1 positive tumors.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study of Pembrolizumab Versus Docetaxel in Participants Previously Treated for Non-Small Cell Lung Cancer (MK-3475-033/KEYNOTE-033)
  • Official Title: A Multinational, Multicenter, Phase III, Randomized Open-label Trial of Pembrolizumab Versus Docetaxel in Previously Treated Subjects With Non-Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: 3475-033
  • SECONDARY ID: MK-3475-033
  • SECONDARY ID: KEYNOTE-033
  • NCT ID: NCT02864394

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
PembrolizumabKEYTRUDA®, MK-3475Pembrolizumab
DocetaxelTAXOTERE®Docetaxel

Purpose

The purpose of this study is to assess the efficacy of pembrolizumab (MK-3475) versus docetaxel in participants with non-small cell lung cancer (NSCLC) with programmed cell death ligand 1 (PD-L1) positive tumors who have experienced disease progression after platinum-containing systemic therapy. The primary hypotheses of this study are that pembrolizumab (MK-3475) prolongs overall survival (OS) and that pembrolizumab prolongs progression-free survival (PFS), compared to docetaxel in participants with PD-L1 positive tumors.

Trial Arms

NameTypeDescriptionInterventions
PembrolizumabExperimentalParticipants with NSCLC receive pembrolizumab 2 mg/kg intravenously (IV) over 30 minutes every 3 weeks (Q3W) for up to 35 doses (approximately 24 months).
  • Pembrolizumab
DocetaxelExperimentalParticipants with NSCLC receive Docetaxel 75 mg/m^2 IV over 1 hour Q3W until disease progression, toxicity, investigator's decision to discontinue, or consent withdrawal.
  • Docetaxel

Eligibility Criteria

        Inclusion Criteria:

          -  Chinese participants must be born, raised, and reside in China

          -  Has a histologically or cytologically confirmed diagnosis of stage IIIB/IV or
             recurrent NSCLC and have at least one measurable lesion as defined by RECIST 1.1

          -  Has a life expectancy of ≥3 months

          -  Has progression of disease (investigator determined) per RECIST 1.1 after treatment
             with at least two cycles of a platinum-containing doublet

          -  Has documentation of epidermal growth factor receptor (EGFR) mutation and anaplastic
             lymphoma kinase (ALK) translocation status

          -  Participants with an EGFR sensitizing mutation tumor will be excluded

          -  Has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 10
             days prior to study start

          -  Has provided archival tumor tissue sample or newly obtained formalin fixed tumor
             tissue from a recent biopsy of a tumor lesion not previously irradiated

          -  Has a PD-L1 positive tumor as determined by immunohistochemistry at a central
             laboratory

          -  Has resolution of toxic effect(s) of the most recent prior chemotherapy to Grade 1 or
             less (except alopecia)

          -  Has recovered from the toxicity and/or complications of any recent major surgery or
             radiation therapy

          -  Females must not be pregnant (negative urine or serum human chorionic gonadotropin
             test within 72 hours prior to receiving the first dose of study medication)

          -  Female and male participants of reproductive potential must agree to use adequate
             contraception starting with the first dose of study therapy through 120 days after the
             last dose of pembrolizumab (MK-3475) or 180 days after the last dose of docetaxel

        Exclusion Criteria:

          -  Has received prior therapy with docetaxel for NSCLC

          -  Is currently participating or has participated in a study of an investigational agent
             or using an investigational device within 4 weeks of the first dose of study treatment

          -  Is receiving systemic steroid therapy within 3 days prior to the first dose of study
             treatment or receiving any other form of immunosuppressive

          -  Is expected to require any other form of systemic or localized antineoplastic therapy
             while on study including maintenance therapy with another agent for NSCLC or radiation
             therapy

          -  Has received prior systemic cytotoxic chemotherapy, antineoplastic biological therapy
             (e.g., cetuximab), any other agents used as systemic treatment for cancer, or major
             surgery within 3 weeks of the first dose of study treatment; received thoracic
             radiation therapy of > 30 Gray Units (Gy) within 6 months of the first dose of study
             treatment; received prior ALK-directed tyrosine kinase inhibitor therapy or completed
             palliative radiotherapy of 30 Gy or less within 7 days of the first dose of study
             treatment

          -  Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1),
             anti-PD-L1, anti-PD-L2, with an agent directed to an agonist or antagonist T-cell
             check point receptor, or if the participant has previously participated in Merck
             sponsored clinical trials evaluating pembrolizumab (MK-3475)

          -  Has a known additional malignancy that is progressing or requires active treatment,
             with the exception of early stage cancers, treated with curative intent, basal cell
             carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer,
             or in situ breast cancer that has undergone potentially curative therapy

          -  Has known active central nervous system metastases and/or carcinomatous meningitis

          -  Has active autoimmune disease that has required systemic treatment in past 2 years

          -  Has had an allogeneic tissue/solid organ transplant

          -  Has a history of (non-infectious) pneumonitis that required steroids or current
             pneumonitis

          -  Has received or will receive a live vaccine within 30 days prior to the first
             administration of study medication

          -  Has an active infection requiring intravenous systemic therapy

          -  Has known history of Human Immunodeficiency Virus (HIV) (HIV ½ antibodies)

          -  Has known active Hepatitis B or C

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial

          -  Is, at the time of signing informed consent, a regular user (including "recreational
             use") of any illicit drugs or had a recent history (within the last year) of substance
             abuse (including alcohol)

          -  Is pregnant or breastfeeding, or expecting to conceive or father children starting
             with the screening visit (Visit 1) through 120 days after the last dose of
             pembrolizumab (MK-3475) or 180 days after the last dose of docetaxel

          -  Requires treatment with a strong inhibitor of Cytochrome P450 3A4
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival (OS) in Participants With Programmed Cell Death Ligand 1 (PD-L1) Positive (Tumor Proportion Score [TPS] ≥50%) Tumors
Time Frame:Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)
Safety Issue:
Description:OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS was reported by treatment arm for participants in the TPS ≥50% stratum of PD-L1 expression.

Secondary Outcome Measures

Measure:Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥50%) Tumors
Time Frame:Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)
Safety Issue:
Description: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) per RECIST 1.1. as assessed by BICR. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for participants in the TPS ≥50% stratum of PD-L1 expression.
Measure:ORR Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants)
Time Frame:Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)
Safety Issue:
Description:ORR was defined as the percentage of participants in the analysis population who had a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by BICR. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for participants in the TPS ≥1% stratum of PD-L1 expression (all participants).
Measure:Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥50%) Tumors
Time Frame:Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)
Safety Issue:
Description:For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 based upon BICR, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death, whichever occurred first. 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 at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, DOR was reported by treatment arm for participants in the TPS ≥50% stratum of PD-L1 expression.
Measure:DOR Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants)
Time Frame:Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)
Safety Issue:
Description:For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 based upon BICR, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death, whichever occurred first. 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 at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, DOR was reported by treatment arm for participants in the TPS ≥1% stratum of PD-L1 expression (all participants).
Measure:Number of Participants Who Experienced an Adverse Event (AE)
Time Frame:Up to approximately 29 months
Safety Issue:
Description:An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, 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 of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. Per protocol, the number of participants who experienced an AE was reported by treatment arm for all participants (TPS ≥1% stratum of PD-L1 expression) as part of the pre-specified secondary safety analysis (Final Analysis cut-off date of 09-Sep-2019).
Measure:Number of Participants Who Discontinued Study Treatment Due to an AE
Time Frame:Up to approximately 26 months
Safety Issue:
Description:An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, 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 of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. Per protocol, the number of participants who discontinued study treatment due to an AE was reported by treatment arm for all participants (TPS ≥1% stratum of PD-L1 expression) as part of the pre-specified secondary safety analysis (Final Analysis cut-off date of 09-Sep-2019).

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

  • Programmed Cell Death-1 (PD1, PD-1)
  • Programmed Death-Ligand 1 (PDL1, PD-L1)

Last Updated

October 5, 2020