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

Non-small Cell Lung Cancer Clinical Trial

Official title:

A Randomized, Double-Blind, Phase III Study of Carboplatin-Paclitaxel/Nab-Paclitaxel Chemotherapy With or Without Pembrolizumab (MK-3475) in First Line Metastatic Squamous Non-small Cell Lung Cancer Subjects (KEYNOTE-407)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03875092
• Other study ID #: 3475-407 China Extension
• Secondary ID: 173568MK-3475-40
• Status: Completed
• Phase: Phase 3
• Start date: April 21, 2017
• Est. completion date: September 14, 2023

Study information

• Verified date: September 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this China extension study, carboplatin and paclitaxel or nano particle albumin-bound paclitaxel (nab-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.

Description:

The MK-3475-407-China Extension Study has enrolled a total of 125 participants, of which 15 participants have been also previously enrolled in the MK-3475-407 global study (NCT02775435).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 125
• Est. completion date: September 14, 2023
• Est. primary completion date: September 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

• Has participated in any other pembrolizumab trial and has been treated with pembrolizumab.

• Has an active infection requiring therapy.

• Has known history of Human Immunodeficiency Virus (HIV).

• Has known active Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection.

• Is, at the time of providing documented informed consent, a regular user (including "recreational use") of any illicit drugs or has a recent history (within the last year) of substance abuse (including alcohol).

• Has interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Biological:
• Pembrolizumab
IV infusion

Drug:
• Paclitaxel
IV infusion
• Nab-paclitaxel
IV infusion
• Carboplatin
IV infusion Carboplatin dose should not exceed 900 mg.
• Saline placebo for pembrolizumab
IV infusion

Locations

Country	Name	City	State
China	Zhongshan Hospital Fudan University	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Country where clinical trial is conducted

China, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 (Database cutoff date of 30-Sep-2020)
Primary	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 (Database cutoff date of 30-Sep-2020)
Secondary	Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed by RECIST 1.1. ORR as assessed by blinded independent central review per RECIST 1.1 is presented.	Up to approximately 33 months (Database cutoff date of 30-Sep-2020)
Secondary	Duration of Response (DOR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	For participants who demonstrated a confirmed response (Complete Response [CR]: Disappearance of all target lesions or Partial Response [PR]: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression as assessed by RECIST 1.1 or death. DOR as assessed by blinded independent central review per RECIST 1.1 is presented.	Up to approximately 30 months (Database cutoff date of 30-Sep-2020)
Secondary	Number of Participants Who Experienced an Adverse Event (AE)	An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE is presented. Data are from the product-limit (Kaplan-Meier) method for censored data.	Up to approximately 31 months (Database cutoff date of 30-Sep-2020)
Secondary	Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)	The number of participants who discontinued study treatment due to an AE is presented.	Up to approximately 29 months (Database cutoff date of 30-Sep-2020)

External Links

•   Merck Clinical Trials Information