Study of Pembrolizumab (MK-3475) Compared to Platinum-Based Chemotherapies in Participants With Metastatic Non-Small Cell Lung Cancer (MK-3475-024/KEYNOTE-024)

NCT ID: NCT02142738

Last Updated: 2022-06-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 305 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-08-25
• Study Completion Date: 2021-05-27

Brief Summary

This is a study to assess the efficacy and safety of pembrolizumab (MK-3475/SCH 900475) compared to standard of care (SOC) platinum-based chemotherapies in the treatment of participants with previously untreated stage IV, programmed cell death ligand 1 (PD-L1) strong expressing Non-Small Cell Lung Cancer (NSCLC). The primary hypothesis of this study is that participants with PD-L1 strong NSCLC will have a longer Progression Free Survival (PFS), as assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) when treated with pembrolizumab than when treated with SOC platinum-based chemotherapies.

With Amendment 09 (20 December 2017), once participants have achieved the study objective or the study has ended, participants will be discontinued from this study and enrolled in an extension study to continue protocol-defined assessments and treatment.

Detailed Description

Treatment Phase: Participants randomized to pembrolizumab will be treated for up to 35 cycles or until documented progressive disease (PD) occurs. Participants randomized to SOC chemotherapies will be treated with their randomized study drug for up to 4-6 cycles. After this, participants with non-squamous histologies may choose to be treated with maintenance pemetrexed for the remainder of the study or until disease progression, unacceptable adverse event(s) (AEs), intercurrent illness that prevents further administration of treatment, investigator's decision to withdraw the participant, noncompliance with study treatment or procedures requirements, the participant receives 35 treatments of study treatment (pembrolizumab arm only), or administrative reasons. Participants receiving pembrolizumab who stop drug administration after receiving 35 study treatments for reasons other than disease progression or intolerability, or participants who attain a complete response and stop study treatment may be eligible for retreatment with pembrolizumab upon experiencing disease progression. The decision to retreat with a second course of pembrolizumab will be at the discretion of the Investigator only if participants meet the criteria for retreatment and the study is ongoing. Retreatment (second course) is limited to 17 cycles. Participants randomized to receive SOC chemotherapy may be eligible to receive pembrolizumab if criteria to switch are met.

Switch-Over Phase: This is only applicable for participants randomized to receive SOC. Eligible participants will be treated with pembrolizumab for the remainder of the study or until disease progression, unacceptable AEs, intercurrent illness that prevents further administration of treatment, investigator's decision to withdraw the participant, noncompliance with study treatment or procedures requirements, the participant receives 35 treatments of study treatment (pembrolizumab arm only), or administrative reasons.

Conditions

Non-Small Cell Lung Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pembrolizumab

Participants receive pembrolizumab 200 mg, administered as intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 35 cycles.

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab IV solution

Paclitaxel+Carboplatin

Participants receive paclitaxel 200 mg/m\^2 and carboplatin Area Under the Curve (AUC) 5 or 6, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles followed by optional pemetrexed 500 mg/m\^2 every three weeks (Q3W) maintenance for participants with non-squamous histologies for the remainder of the study or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.

Group Type: ACTIVE_COMPARATOR

Paclitaxel

Intervention Type: DRUG

Paclitaxel IV solution

Carboplatin

Intervention Type: DRUG

Carboplatin IV solution

Pemetrexed

Intervention Type: DRUG

Pemetrexed Lyophilized Powder for Infusion

Pemetrexed+Carboplatin

Participants receive pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6, IV infusion on Day 1 of each 21-day cycle for 4-6 cycles; participants with non-squamous histologies may then receive pemetrexed 500 mg/m\^2 on Day 1 of each 21-day cycle as maintenance therapy for the remainder of the study or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.

Group Type: ACTIVE_COMPARATOR

Carboplatin

Intervention Type: DRUG

Carboplatin IV solution

Pemetrexed

Intervention Type: DRUG

Pemetrexed Lyophilized Powder for Infusion

Pemetrexed+Cisplatin

Participants receive pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles followed by optional pemetrexed 500 mg/m\^2 Q3W maintenance for the remainder of the study or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.

Group Type: ACTIVE_COMPARATOR

Pemetrexed

Intervention Type: DRUG

Pemetrexed Lyophilized Powder for Infusion

Cisplatin

Intervention Type: DRUG

Cisplatin IV solution

Gemcitabine+Carboplatin

Participants receive gemcitabine 1250 mg/m\^2, administered as IV infusion on Days 1 and 8 of each 21-day cycle and carboplatin AUC 5 or 6, administered as IV infusion on Day 1 of a 21-day cycle, for 4-6 cycles or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.

Group Type: ACTIVE_COMPARATOR

Carboplatin

Intervention Type: DRUG

Carboplatin IV solution

Gemcitabine

Intervention Type: DRUG

Gemcitabine Lyophilized Powder for Infusion

Gemcitabine+Cisplatin

Participants receive gemcitabine 1250 mg/m\^2, administered as IV infusion on Days 1 and 8 of each 21-day cycle and cisplatin 75 mg/m\^2, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles or until documented PD or participant discontinuation. If PD occurs, participants may be able to receive pembrolizumab Q3W in a second course of treatment.

Group Type: ACTIVE_COMPARATOR

Cisplatin

Intervention Type: DRUG

Cisplatin IV solution

Gemcitabine

Intervention Type: DRUG

Gemcitabine Lyophilized Powder for Infusion

Interventions

Pembrolizumab

Pembrolizumab IV solution

Intervention Type: DRUG

Paclitaxel

Paclitaxel IV solution

Intervention Type: DRUG

Carboplatin

Carboplatin IV solution

Intervention Type: DRUG

Pemetrexed

Pemetrexed Lyophilized Powder for Infusion

Intervention Type: DRUG

Cisplatin

Cisplatin IV solution

Intervention Type: DRUG

Gemcitabine

Gemcitabine Lyophilized Powder for Infusion

Intervention Type: DRUG

Other Intervention Names

MK-3475; SCH 900475; KEYTRUDA®

Eligibility Criteria

Inclusion Criteria

• Histological or cytological diagnosis of Stage IV NSCLC lacking epidermal growth factor receptor (EGFR)-sensitizing mutation and/or anaplastic lymphoma kinase (ALK) translocation, and received no prior systemic chemotherapy treatment for their metastatic NSCLC
• At least one radiographically measurable lesion per RECIST 1.1
• Life expectancy of at least 3 months
• Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status
• Adequate organ function
• No history of prior malignancy, with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or in situ cervical cancer, or has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy
• Provided newly obtained formalin fixed tumor tissue from a biopsy of a tumor at the time of or AFTER the diagnosis of metastatic disease has been made AND from a site not previously irradiated
• PD-L1 strong expressing tumor as determined by immunohistochemistry (IHC) at a central laboratory
• Female participants must have a negative pregnancy test at screening if of childbearing potential or be of non-childbearing potential
• Female participants of childbearing potential and male partners with female partners of childbearing potential must agree to use 2 adequate barrier methods of contraception during the study and for 120 days after last dose of study drug and up to 180 days after last dose of chemotherapy

Exclusion Criteria

• EGFR sensitizing mutation and/or ALK translocation
• Has received systemic therapy for the treatment of their stage IV NSCLC. Completion of treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic disease.
• Currently participating or has participated in a study of an investigational agent or using an investigational device within 4 weeks of first dose of study drug
• Tumor specimen is not evaluable for PD-L1 expression by the central laboratory
• Receiving systemic steroid therapy < 3 days prior to first dose of study drug or receiving any other form of immunosuppressive medication
• Expected to require any other form of systemic or localized antineoplastic therapy during the study
• Received prior systemic cytotoxic chemotherapy, biological therapy, major surgery within 3 weeks of first dose of study drug; received thoracic radiation therapy of > 30 gray (Gy) within 6 months of first dose of study drug
• Received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-PD-L1, anti-programmed cell death-ligand 2 (anti-PD-L2), anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor [TNFR] family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
• Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
• Active autoimmune disease that has required systemic treatment in past 2 years
• Allogenic tissue/solid organ transplant
• Interstitial lung disease or pneumonitis that has required oral or IV steroids
• Received or will receive a live vaccine within 30 days prior to first dose of study drug
• Active infection requiring IV systemic therapy
• Known history of human immunodeficiency virus (HIV)
• Known active tuberculosis, or hepatitis B or C
• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
• 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)
• Pregnant or breastfeeding, or expecting to conceive or father children during the study and through 120 days after last dose of pembrolizumab or 180 days after last dose of SOC chemotherapy
• Immediate family member who is investigational site or sponsor staff directly involved with this study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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Reference Type: RESULT

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Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://merckoncologyclinicaltrials.com

Merck Oncology Clinical Trial Information

Other Identifiers

142728

Identifier Type: REGISTRY

Identifier Source: secondary_id

MK-3475-024

Identifier Type: OTHER

Identifier Source: secondary_id

2014-000323-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

3475-024

Identifier Type: -

Identifier Source: org_study_id