NCT02775435 · CITED IN SOURCE DOCUMENTS

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)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2024-10-08

This is a study of carboplatin and paclitaxel or nano particle albumin-bound paclitaxel (nab-paclitaxel) with or without pembrolizumab (MK-3475, KEYTRUDA®) in 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). 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.

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What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Number of Participants Who Experienced an Adverse Event (AE)

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outcome · POSTED

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

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Has a histologically or cytologically confirmed diagnosis of stage IV (M1a or M1b-American Joint Committee on Cancer \[AJCC\] 7th edition) 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 drug. * 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 drug through 95 days after the last dose of study drug. 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 Gy within 6 months of the first dose of study drug. * Completed palliative radiotherapy within 7 days of the first dose of study drug. * 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 or C. Active Hepatitis B. * 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.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Participants receive pembrolizumab 200 mg by intravenous (IV) infusion prior to chemotherapy on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles (\~ 2 years) PLUS Investigator's choice of paclitaxel (200 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m\^2 by IV infusion on Days 1, 8, 15 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.
intervention Names
Biological: Pembrolizumab
Drug: Paclitaxel
Drug: Nab-paclitaxel
Drug: Carboplatin
label
Pembrolizumab + Chemotherapy Combo
type
EXPERIMENTAL
description
Participants receive normal saline as placebo by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles (\~ 2 years) PLUS Investigator's choice of paclitaxel (200 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m\^2 by IV infusion on Days 1, 8, 15 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.
intervention Names
Drug: Paclitaxel
Drug: Nab-paclitaxel
Drug: Carboplatin
Drug: Saline placebo for pembrolizumab
label
Placebo + Chemotherapy
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Pembrolizumab + Chemotherapy Combo
description
IV infusion
name
Pembrolizumab
other Names
MK-3475
KEYTRUDA®
type
BIOLOGICAL
arm Group Labels
Pembrolizumab + Chemotherapy Combo
Placebo + Chemotherapy
description
IV infusion
name
Paclitaxel
other Names
TAXOL®
type
DRUG
arm Group Labels
Pembrolizumab + Chemotherapy Combo
Placebo + Chemotherapy
description
IV infusion
name
Nab-paclitaxel
other Names
ABRAXANE®
type
DRUG
arm Group Labels
Pembrolizumab + Chemotherapy Combo
Placebo + Chemotherapy
description
IV infusion Carboplatin dose should not to exceed 900 mg.
name
Carboplatin
other Names
PARAPLATIN®
type
DRUG
arm Group Labels
Placebo + Chemotherapy
description
IV infusion
name
Saline placebo for pembrolizumab
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: TRIPLE
who Masked: PARTICIPANT
INVESTIGATOR
OUTCOMES_ASSESSOR

primary Purpose

TREATMENT

Enrollment

count: 559
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
time Frame
Up to approximately 19 months
description
OS was defined as the time from randomization to death due to any cause. OS is presented.
measure
Overall Survival (OS)
time Frame
Up to approximately 19 months

secondary Outcomes

description
ORR was defined as the percentage of participants 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.
measure
Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
time Frame
Up to approximately 19 months
description
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.
measure
Duration of Response (DOR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
time Frame
Up to approximately 19 months
description
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change infrequency and/or intensity) of a preexisting condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced an AE is presented.
measure
Number of Participants Who Experienced an Adverse Event (AE)
time Frame
Up to approximately 83 months
description
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change infrequency and/or intensity) of a preexisting condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE was presented.
measure
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
time Frame
Up to approximately 29 months

Full study description

brief Summary: This is a study of carboplatin and paclitaxel or nano particle albumin-bound paclitaxel (nab-paclitaxel) with or without pembrolizumab (MK-3475, KEYTRUDA®) in 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). 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.

Source references

references

citation
Garassino MC, Cheng Y, Rodriguez-Abreu D, Novello S, Mazieres J, Robinson AG, Powell SF, Halmos B, Gray JE, Wang M, Chen C, Yang J, Souza F, Schwarzenberger P, Paz-Ares L. Impact of Tumor Response and Response Duration on Survival Among Participants Receiving Pembrolizumab Plus Chemotherapy as First-Line Therapy for Non-Small-Cell Lung Cancer. Oncol Ther. 2025 Sep;13(3):667-681. doi: 10.1007/s40487-025-00350-6. Epub 2025 Jun 11.
pmid
40498298
type
DERIVED
citation
Gadgeel SM, Rodriguez-Abreu D, Halmos B, Garassino MC, Kurata T, Cheng Y, Jensen E, Shamoun M, Rajagopalan K, Paz-Ares L. Pembrolizumab Plus Chemotherapy for Metastatic NSCLC With Programmed Cell Death Ligand 1 Tumor Proportion Score Less Than 1%: Pooled Analysis of Outcomes After Five Years of Follow-Up. J Thorac Oncol. 2024 Aug;19(8):1228-1241. doi: 10.1016/j.jtho.2024.04.011. Epub 2024 Apr 18.
pmid
38642841
type
DERIVED
citation
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pmid
37465924
type
DERIVED
citation
Garassino MC, Gadgeel S, Novello S, Halmos B, Felip E, Speranza G, Hui R, Garon EB, Horinouchi H, Sugawara S, Rodriguez-Abreu D, Reck M, Cristescu R, Aurora-Garg D, Loboda A, Lunceford J, Kobie J, Ayers M, Piperdi B, Pietanza MC, Paz-Ares L. Associations of Tissue Tumor Mutational Burden and Mutational Status With Clinical Outcomes With Pembrolizumab Plus Chemotherapy Versus Chemotherapy For Metastatic NSCLC. JTO Clin Res Rep. 2022 Nov 8;4(1):100431. doi: 10.1016/j.jtocrr.2022.100431. eCollection 2023 Jan.
pmid
36793385
type
DERIVED
citation
Novello S, Kowalski DM, Luft A, Gumus M, Vicente D, Mazieres J, Rodriguez-Cid J, Tafreshi A, Cheng Y, Lee KH, Golf A, Sugawara S, Robinson AG, Halmos B, Jensen E, Schwarzenberger P, Pietanza MC, Paz-Ares L. Pembrolizumab Plus Chemotherapy in Squamous Non-Small-Cell Lung Cancer: 5-Year Update of the Phase III KEYNOTE-407 Study. J Clin Oncol. 2023 Apr 10;41(11):1999-2006. doi: 10.1200/JCO.22.01990. Epub 2023 Feb 3.
pmid
36735893
type
DERIVED
citation
Paz-Ares L, Vicente D, Tafreshi A, Robinson A, Soto Parra H, Mazieres J, Hermes B, Cicin I, Medgyasszay B, Rodriguez-Cid J, Okamoto I, Lee S, Ramlau R, Vladimirov V, Cheng Y, Deng X, Zhang Y, Bas T, Piperdi B, Halmos B. A Randomized, Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous NSCLC: Protocol-Specified Final Analysis of KEYNOTE-407. J Thorac Oncol. 2020 Oct;15(10):1657-1669. doi: 10.1016/j.jtho.2020.06.015. Epub 2020 Jun 26.
pmid
32599071
type
DERIVED
citation
Mazieres J, Kowalski D, Luft A, Vicente D, Tafreshi A, Gumus M, Laktionov K, Hermes B, Cicin I, Rodriguez-Cid J, Wilson J, Kato T, Ramlau R, Novello S, Reddy S, Kopp HG, Piperdi B, Li X, Burke T, Paz-Ares L. Health-Related Quality of Life With Carboplatin-Paclitaxel or nab-Paclitaxel With or Without Pembrolizumab in Patients With Metastatic Squamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2020 Jan 20;38(3):271-280. doi: 10.1200/JCO.19.01348. Epub 2019 Nov 21.
pmid
31751163
type
DERIVED
citation
Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gumus M, Mazieres J, Hermes B, Cay Senler F, Csoszi T, Fulop A, Rodriguez-Cid J, Wilson J, Sugawara S, Kato T, Lee KH, Cheng Y, Novello S, Halmos B, Li X, Lubiniecki GM, Piperdi B, Kowalski DM; KEYNOTE-407 Investigators. Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N Engl J Med. 2018 Nov 22;379(21):2040-2051. doi: 10.1056/NEJMoa1810865. Epub 2018 Sep 25.
pmid
30280635
type
DERIVED