Clinical trial NCT02864394: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2016-08-12
Enrollment: 425
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


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

Primary outcomes:
measure: Overall Survival (OS) in Participants With Programmed Cell Death Ligand 1 (PD-L1) Positive (Tumor Proportion Score [TPS] ≥50%) Tumors
timeFrame: Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)
measure: OS in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants)
timeFrame: Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)
measure: Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With PD-L1 Positive (TPS ≥50%) Tumors
timeFrame: Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)
measure: PFS Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants)
timeFrame: Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)
Secondary outcomes:
measure: Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥50%) Tumors
timeFrame: Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)
measure: ORR Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants)
timeFrame: Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)
measure: Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥50%) Tumors
timeFrame: Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)
measure: DOR Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants)
timeFrame: Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to approximately 66 months
measure: Number of Participants Who Discontinued Study Treatment Due to an AE
timeFrame: Up to approximately 45 months
measure: Number of Participants Who Experienced an Adverse Event of Special Interest (AEOSI)
timeFrame: Up to approximately 66 months
measure: Number of Participants Who Experienced a Grade 3-5 AE
timeFrame: Up to approximately 66 months
measure: Number of Participants Who Experienced an AE That Was Experienced by ≥10% of Participants in Either Arm
timeFrame: Up to approximately 66 months
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Ren S, Feng J, Ma S, Chen H, Ma Z, Huang C, Zhang L, He J, Wang C, Zhou J, Danchaivijtr P, Wang CC, Vynnychenko I, Wang K, Orlandi F, Sriuranpong V, Li B, Ge J, Dang T, Zhou C. KEYNOTE-033: Randomized phase 3 study of pembrolizumab vs docetaxel in previously treated, PD-L1-positive, advanced NSCLC. Int J Cancer. 2023 Aug 1;153(3):623-634. doi: 10.1002/ijc.34532. Epub 2023 May 4.