Study of Pembrolizumab (MK-3475) Versus Platinum-Based Chemotherapy for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Advanced or Metastatic Non-Small Cell Lung Cancer (MK-3475-042/KEYNOTE-042)-China Extension Study

NCT ID: NCT03850444

Last Updated: 2023-09-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 262 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-01
• Study Completion Date: 2022-09-08

Brief Summary

In the China extension study, Chinese participants with programmed cell death ligand 1 (PD-L1)-positive non-small cell lung cancer (NSCLC) will be randomized to receive single agent pembrolizumab for up to 35 treatments or standard of care (SOC) platinum-based chemotherapy (carboplatin + paclitaxel or carboplatin + pemetrexed for 4 to 6 21-day cycles). Chinese participants in the platinum-based chemotherapy arms with non-squamous tumor histologies may receive pemetrexed maintenance therapy after the 4 to 6 cycles of chemotherapy. The primary extension study hypothesis is that pembrolizumab prolongs overall survival (OS) compared to SOC chemotherapy in Chinese participants.

Detailed Description

The China extension study enrolled 262 participants. Of the 262 total participants enrolled, 92 were also previously enrolled in the global study for MK-3475-042 (NCT02220894).

Conditions

Non-small Cell Lung Cancer

Study Design

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

Study Groups

Pembrolizumab

Participants receive pembrolizumab 200 mg by IV infusion on Day 1 every 3 weeks (Q3W) for a maximum of 35 cycles (21-day cycles). Participants who stop the initial course of pembrolizumab due to complete response or complete the initial course of pembrolizumab and have stable disease, but progress after discontinuation, are eligible for a second course of pembrolizumab for up to an additional 1 year (17 additional 21-day cycles).

Group Type: EXPERIMENTAL

pembrolizumab

Intervention Type: BIOLOGICAL

SOC Treatment

Participants receive carboplatin at target dose Area Under the Curve (AUC 5) (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m\^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m\^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies receive optional additional maintenance treatment with pemetrexed 500 mg/m\^2 by IV infusion on Day 1 Q3W.

Group Type: ACTIVE_COMPARATOR

carboplatin

Intervention Type: DRUG

paclitaxel

Intervention Type: DRUG

pemetrexed

Intervention Type: DRUG

Interventions

pembrolizumab

Intervention Type: BIOLOGICAL

carboplatin

Intervention Type: DRUG

paclitaxel

Intervention Type: DRUG

pemetrexed

Intervention Type: DRUG

Other Intervention Names

MK-3475; KEYTRUDA®; PARAPLATIN®; TAXOL®; ALIMTA®

Eligibility Criteria

Inclusion Criteria

• Histologically- or cytologically-confirmed diagnosis of advanced or metastatic NSCLC
• PD-L1 positive tumor
• Measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Life expectancy of at least 3 months
• No prior systemic chemotherapy for the treatment of the participant's advanced or metastatic disease (treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as completed at least 6 months prior to diagnosis of advanced or metastatic disease)
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Adequate organ function
• No prior malignancy, with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or in situ cancer, or has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy
• Submission of formalin-fixed diagnostic tumor tissue (in the case of participants having received adjuvant systemic therapy, the tissue should be taken after completion of this therapy)
• Female participants of childbearing potential must have a negative urine or serum pregnancy test and must be willing to use two adequate barrier methods of contraception or a barrier method plus a hormonal method starting with the screening visit through 120 days after the last dose of pembrolizumab or 180 days after the last dose of chemotherapeutic agents used in the study
• Male participants with a female partner(s) of childbearing potential must be willing to use two adequate barrier methods of contraception from screening through 120 days after the last dose of pembrolizumab or 180 days after the last dose of chemotherapeutic agents used in the study

Exclusion Criteria

• Epidermal growth factor receptor (EGFR)-sensitizing mutation and/or is echinoderm microtubule-associated protein-like 4 (EML4) gene/anaplastic lymphoma kinase (ALK) gene fusion positive
• 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 therapy
• No tumor specimen evaluable for PD-L1 expression by the central study laboratory
• Squamous histology and received carboplatin in combination with paclitaxel in the adjuvant setting
• Is receiving systemic steroid therapy ≤3 days prior to the first dose of study therapy or receiving any other form of immunosuppressive medication with the exception of daily steroid replacement therapy
• The NSCLC can be treated with curative intent with either surgical resection and/or chemoradiation
• Expected to require any other form of systemic or localized antineoplastic therapy while on study
• Any prior systemic cytotoxic chemotherapy, biological therapy or major surgery within 3 weeks of the first dose of study therapy; received lung radiation therapy >30 Gy within 6 months of the first dose of study therapy
• Prior therapy with an anti-PD-1, anti-PD-L1, anti-PDL2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
• Known central nervous system metastases and/or carcinomatous meningitis
• Active autoimmune disease that has required systemic treatment in the past 2 years
• Had allogeneic tissue/solid organ transplantation
• Interstitial lung disease or history of pneumonitis that has required oral or IV steroids
• Has received or will receive a live vaccine within 30 days prior to the first study therapy (seasonal flu vaccines that do not contain live vaccine are permitted)
• Active infection requiring intravenous systemic therapy
• Known history of human immunodeficiency virus (HIV)
• Known active Hepatitis B or C
• Regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol)
• Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the 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

Wu YL, Zhang L, Fan Y, Zhou J, Zhang L, Zhou Q, Li W, Hu C, Chen G, Zhang X, Zhou C, Dang T, Sadowski S, Kush DA, Zhou Y, Li B, Mok T. Randomized clinical trial of pembrolizumab vs chemotherapy for previously untreated Chinese patients with PD-L1-positive locally advanced or metastatic non-small-cell lung cancer: KEYNOTE-042 China Study. Int J Cancer. 2021 May 1;148(9):2313-2320. doi: 10.1002/ijc.33399. Epub 2020 Dec 9.

Reference Type: RESULT

PMID: 33231285 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.merckclinicaltrials.com

Merck Clinical Trials Information

Other Identifiers

152877

Identifier Type: OTHER

Identifier Source: secondary_id

MK-3475-042

Identifier Type: OTHER

Identifier Source: secondary_id

KEYNOTE-042

Identifier Type: OTHER

Identifier Source: secondary_id

3475-042 China Extension

Identifier Type: -

Identifier Source: org_study_id