A Study of Carboplatin-Paclitaxel/Nab-Paclitaxel Chemotherapy With or Without Pembrolizumab (MK-3475) in Adults With First Line Metastatic Squamous Non-small Cell Lung Cancer (MK-3475-407/KEYNOTE-407)-China Extension Study

NCT03875092 | Completed Phase 3 Results DMC FDA Drug

• 4 other identifiers: 3475-407 China Extension173568MK-3475-407KEYNOTE-407
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 1

Brief Summary

In this China extension study, carboplatin and paclitaxel with or without pembrolizumab (MK-3475, KEYTRUDA®) will be administered to Chinese adults with first line metastatic squamous non-small cell lung cancer (NSCLC). The primary hypotheses are that treatment with pembrolizumab prolongs: 1) Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by a blinded central imaging vendor compared to placebo, and 2) Overall Survival (OS) in Chinese participants. After analysis of interim results was conducted, the protocol was amended (Amendment 5) to allow participants the option to discontinue placebo in the control arm and to switch to pembrolizumab in the event of documented progressive disease as assessed by central review.

Conditions

Non-small Cell Lung Cancer

Keywords

Programmed Cell Death-1 (PD1, PD-1); Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1); Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)

Outcome Measures

Primary Outcomes (2)

• Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

  PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1), PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of ≥1 new lesions was also considered PD. PFS as assessed by blinded independent central review per RECIST 1.1 is presented. Data are from the product-limit (Kaplan-Meier) method for censored data.

  Up to approximately 33 months

• Overall Survival (OS)

  OS was defined as the time from randomization to death due to any cause. OS is presented. Data are from the product-limit (Kaplan-Meier) method for censored data.

  Up to approximately 39 months

Secondary Outcomes (4)

• Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

  Up to approximately 33 months

• Duration of Response (DOR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

  Up to approximately 30 months

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

  Up to approximately 31 months

• Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)

  Up to approximately 29 months

Study Arms (2)

Pembrolizumab + Chemotherapy

EXPERIMENTAL

Participants receive pembrolizumab 200 mg by intravenous (IV) infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS paclitaxel (200 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) PLUS carboplatin Area Under the Curve (AUC) 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.

Biological: Pembrolizumab; Drug: Paclitaxel; Drug: Carboplatin

Chemotherapy

ACTIVE COMPARATOR

Participants receive normal saline by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS paclitaxel (200 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.

Drug: Paclitaxel; Drug: Carboplatin; Drug: Saline placebo for pembrolizumab

Interventions

Pembrolizumab BIOLOGICAL

IV infusion

Also known as: MK-3475, KEYTRUDA®

Pembrolizumab + Chemotherapy

Paclitaxel DRUG

IV infusion

Also known as: TAXOL®

Chemotherapy; Pembrolizumab + Chemotherapy

Carboplatin DRUG

IV infusion Carboplatin dose should not exceed 900 mg.

Also known as: PARAPLATIN®

Chemotherapy; Pembrolizumab + Chemotherapy

Saline placebo for pembrolizumab DRUG

IV infusion

Chemotherapy

Eligibility Criteria

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

You may qualify if:

• Has a histologically or cytologically confirmed diagnosis of stage IV (M1a or M1b-American Joint Committee on Cancer \[AJCC\]) squamous NSCLC.
• Has measurable disease based on RECIST 1.1 as determined by the local site investigator/radiology assessment.
• Has not received prior systemic treatment for metastatic NSCLC.
• Has provided tumor tissue from locations not radiated prior to biopsy.
• Has a life expectancy of at least 3 months.
• Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status.
• Has adequate organ function.
• If female of childbearing potential, is willing to use an adequate method of contraception for the course of the study through 180 days after the last dose of study treatment.
• If male with a female partner(s) of child-bearing potential, must agree to use an adequate method of contraception starting with the first dose of study treatment through 95 days after the last dose of study treatment. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.

You may not qualify if:

• Has non-squamous histology NSCLC.
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to administration of pembrolizumab.
• Before the first dose of study drug: a) Has received prior systemic cytotoxic chemotherapy for metastatic disease; b) Has received other targeted or biological antineoplastic therapy (e.g., erlotinib, crizotinib, cetuximab) for metastatic disease; c) Has had major surgery (\<3 weeks prior to first dose).
• Received radiation therapy to the lung that is \>30 Gray (Gy) within 6 months of the first dose of study treatment.
• Completed palliative radiotherapy within 7 days of the first dose of study treatment.
• Is expected to require any other form of antineoplastic therapy while on study.
• Has received a live-virus vaccination within 30 days of planned treatment start.
• Has a known history of prior malignancy except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has pre-existing peripheral neuropathy that is ≥ Grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) Version 4 criteria.
• Previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody.
• Has a known sensitivity to any component of carboplatin or paclitaxel or nab-paclitaxel.
• Has active autoimmune disease that has required systemic treatment in past 2 years.
• Is on chronic systemic steroids.
• Had prior treatment with any other anti-programmed cell death 1 (anti-PD-1), or programmed cell death ligand 1 (PD-L1) or PD-L2 agent or an antibody or a small molecule targeting other immuno-regulatory receptors or mechanisms.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (1)

Zhongshan Hospital Fudan University

Shanghai, 200032, China

Location

Related Publications (2)

• Cheng Y, Zhang L, Hu J, Wang D, Hu C, Zhou J, Wu L, Cao L, Liu J, Zhang H, Sun H, Wang Z, Gao H, Sun Y, Li B, Hu X, Schwarzenberger P, Paz-Ares L. Pembrolizumab Plus Chemotherapy for Chinese Patients With Metastatic Squamous NSCLC in KEYNOTE-407. JTO Clin Res Rep. 2021 Sep 25;2(10):100225. doi: 10.1016/j.jtocrr.2021.100225. eCollection 2021 Oct.

  PMID: 34661177 RESULT

• Cheng Y, Yang JC, Okamoto I, Zhang L, Hu J, Wang D, Hu C, Zhou J, Wu L, Cao L, Liu J, Zhang H, Sun H, Wang Z, Gao H, Yan Y, Xiao S, Lin J, Pietanza MC, Kurata T. Pembrolizumab plus chemotherapy for advanced non-small-cell lung cancer without tumor PD-L1 expression in Asia. Immunotherapy. 2023 Sep;15(13):1029-1044. doi: 10.2217/imt-2023-0043. Epub 2023 Jul 19.

  PMID: 37465924 DERIVED

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

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

Interventions

pembrolizumab; Paclitaxel; Carboplatin

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; Coordination Complexes

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: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2019
• First Posted: March 14, 2019
• Study Start: April 21, 2017
• Primary Completion: September 30, 2020
• Study Completion: September 14, 2023
• Last Updated: October 1, 2024
• Results First Posted: October 20, 2021

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)