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

NCT02864394 | Completed Phase 3 Results DMC

• 3 other identifiers: 3475-033MK-3475-033KEYNOTE-033
• Study Type: interventional
• Target: 425
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

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

Outcome Measures

Primary Outcomes (4)

• Overall Survival (OS) in Participants With Programmed Cell Death Ligand 1 (PD-L1) Positive (Tumor Proportion Score [TPS] ≥50%) Tumors

  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.

  Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

• OS in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants)

  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 ≥1% stratum of PD-L1 expression (all participants).

  Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

• 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

  PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on BICR, or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters (SOD) 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, PFS was reported by treatment arm for participants in the TPS ≥50% stratum of PD-L1 expression.

  Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

• PFS Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants)

  PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the SOD 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, PFS was reported by treatment arm for participants in the TPS ≥1% stratum of PD-L1 expression (all participants).

  Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

Secondary Outcomes (9)

• Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥50%) Tumors

  Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

• ORR Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants)

  Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

• Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥50%) Tumors

  Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

• DOR Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants)

  Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

• Number of Participants Who Experienced an Adverse Event (AE)

  Up to approximately 66 months

Study Arms (2)

Pembrolizumab

EXPERIMENTAL

Participants with NSCLC receive pembrolizumab 2 mg/kg intravenously (IV) over 30 minutes every 3 weeks (Q3W) for up to 35 doses (approximately 24 months).

Biological: Pembrolizumab

Docetaxel

EXPERIMENTAL

Participants 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.

Drug: Docetaxel

Interventions

Pembrolizumab BIOLOGICAL

Pembrolizumab administered IV at 2 mg/kg on Day 1 of each 21-day cycle for up to 35 doses (approximately 24 months).

Also known as: KEYTRUDA®, MK-3475

Pembrolizumab

Docetaxel DRUG

Docetaxel administered IV at 75 mg/m\^2 on Day 1 of each 21-day cycle as per the approved product label.

Also known as: TAXOTERE®

Docetaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 37141294 RESULT

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Limitations and Caveats

Protocol amendment 5 called for participant discontinuation from this study under protocol-specified circumstances.

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2016
• First Posted: August 12, 2016
• Study Start: September 7, 2016
• Primary Completion: September 9, 2019
• Study Completion: October 14, 2022
• Last Updated: September 19, 2024
• Results First Posted: October 5, 2020

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share