NCT04956692|Active Not RecruitingPhase 3ResultsDMCFDA Drug

Study of Pembrolizumab (MK-3475) Subcutaneous (SC) Versus Pembrolizumab Intravenous (IV) Administered With Platinum Doublet Chemotherapy in Participants With Metastatic Squamous or Nonsquamous Non-Small Cell Lung Cancer (NSCLC) (MK-3475-A86)

A Randomized, Phase 3, Open-label Study to Investigate the Pharmacokinetics and Safety of Subcutaneous Pembrolizumab Versus Intravenous Pembrolizumab, Administered With Platinum Doublet Chemotherapy, in the First-Line Treatment of Participants With Metastatic Squamous or Nonsquamous Non-Small-Cell Lung Cancer

Merck Sharp & Dohme LLC ClinicalTrials.gov

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6 other identifiers

3475-A86MK-3475-A86jRCT20212100322023-508308-40U1111-1298-02152020-002729-27

Study Type

interventional

Target

531

Locations

16 countries

Sites

126

Timeline

RegisteredJul 2021

StartedAug 2021

CompletionOct 2026

Brief Summary

The purpose of this study is to evaluate pembrolizumab (MK-3475) subcutaneous (SC) administration as the first-line therapy in the treatment of metastatic squamous and nonsquamous NSCLC by assessing the pharmacokinetics (PK), safety, and efficacy of pembrolizumab SC injection in combination with standard-of-care chemotherapy. The primary hypothesis of the study is Pembrolizumab SC is noninferior to pembrolizumab intravenous (IV) for Cycle 1 Area Under Curve (AUC) and Cycle 6 minimal concentration (Ctrough) at steady state. Participants who discontinue study treatment after receiving the first course of 35 administrations of pembrolizumab (approximately up to 2 years) for reasons other than disease progression or intolerability, may be eligible for a second course of pembrolizumab for up to approximately 1 additional year if they have experienced radiographic disease progression per RECIST 1.1 as assessed by BICR after stopping first course treatment.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network

Enrollment

531

participants targeted

Target at P50-P75 for phase_3 nonsmall-cell-lung-cancer

Timeline

5mo left

Started Aug 2021

Typical duration for phase_3 nonsmall-cell-lung-cancer

Geographic Reach

16 countries

126 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

5.2 years study duration

Study Progress92%

Aug 2021Oct 2026

First Submitted

Initial submission to the registry

July 6, 2021

Completed

3 days until next milestone

First Posted

Study publicly available on registry

July 9, 2021

Completed

27 days until next milestone

Study Start

First participant enrolled

August 5, 2021

Completed

1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 4, 2023

Completed

1.1 years until next milestone

Results Posted

Study results publicly available

May 17, 2024

Completed

2.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 14, 2026

Expected

Last Updated

December 3, 2024

Status Verified

November 1, 2024

Enrollment Period

1.7 years

First QC Date

July 6, 2021

Results QC Date

March 27, 2024

Last Update Submit

November 14, 2024

Conditions

Non-Small Cell Lung Cancer

Keywords

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

Outcome Measures

Primary Outcomes (2)

Cycle 1 Area Under The Curve From 0-3 Weeks (AUC 0-3wks) of Pembrolizumab
Cycle 1 AUC0-3wks is defined as the area under the concentration-time curve for pembrolizumab in plasma over a 3-week dosing interval in Cycle 1. Each cycle is 21 days.
Cycle 1: predose and postdose day 1; days 2, 3, 4, 5, 6, 7, 10, and 15. Cycle 2: predose day 1. Each cycle is 21 days.
Cycle 6 Model-Based Minimal Concentration (Ctrough) of Pembrolizumab
Cycle 6 model-based Ctrough is defined as the lowest concentration of pembrolizumab in plasma at the end of the dosing interval in Cycle 6, as predicted by the pharmacokinetic (PK) model based on historical intravenous pembrolizumab PK data. Each cycle is 21 days.
Cycle 6: predose day 1; days 2, 3, 4, 5, 6, 7, 10, and 15. Cycle 7: predose day 1. Each cycle is 21 days.

Secondary Outcomes (12)

Objective Response (OR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
Up to approximately 5 years
Cycle 1 Observed Ctrough of Pembrolizumab
Predose Cycle 2 day 1. Each cycle is 21 days.
Cycle 1 Maximum Concentration (Cmax) of Pembrolizumab
Cycle 1: predose day 1; days 2, 3, 4, 5, 6, 7, 10, and 15. Cycle 2: predose day 1. Each cycle is 21 days.
Cycle 6 AUC 0-3wks of Pembrolizumab
Cycle 6: predose and postdose day 1; days 2, 3, 4, 5, 6, 7, 10, and 15. Cycle 7: predose day 1. Each cycle is 21 days.
Cycle 6 Cmax of Pembrolizumab
Cycle 6: predose and postdose day 1; days 2, 3, 4, 5, 6, 7, 10, and 15. Cycle 7: predose day 1. Each cycle is 21 days.
+7 more secondary outcomes

Study Arms (2)

Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy

EXPERIMENTAL

Participants receive pembrolizumab subcutaneous (SC) administration on Day 1 of each cycle (cycle length = 3 weeks) for up to 35 cycles (up to \~2 years) PLUS paclitaxel IV (on Day 1 of each cycle) OR nab-paclitaxel IV (on Days 1, 8, and 15 of each cycle) and carboplatin IV (on Day 1 of each cycle) for 4 cycles for squamous non-small cell lung cancer (NSCLC); PLUS carboplatin IV (on Day 1 of each cycle) Or cisplatin IV (on Day 1 of each cycle) for 4 cycles and pemetrexed IV (on Day 1 of each cycle) until progression, intolerable adverse events, or participant/physician decision for non-squamous NSCLC.

Biological: Pembrolizumab SCDrug: PaclitaxelDrug: Nab-PaclitaxelDrug: CarboplatinDrug: CisplatinDrug: Pemetrexed

Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy

ACTIVE COMPARATOR

Participants receive pembrolizumab intravenous (IV) administration on Day 1 of each cycle (cycle length = 3 weeks) for up to 35 cycles (up to \~2 years) PLUS paclitaxel IV (on Day 1 of each cycle) OR nab-paclitaxel IV (on Days 1, 8, and 15 of each cycle) and carboplatin IV (on Day 1 of each cycle) for 4 cycles for squamous non-small cell lung cancer (NSCLC); PLUS carboplatin IV (on Day 1 of each cycle) Or cisplatin IV (on Day 1 of each cycle) for 4 cycles and pemetrexed IV (on Day 1 of each cycle) until progression, intolerable adverse events, or participant/physician decision for non-squamous NSCLC.

Biological: Pembrolizumab IVDrug: PaclitaxelDrug: Nab-PaclitaxelDrug: CarboplatinDrug: CisplatinDrug: Pemetrexed

Interventions

Pembrolizumab SCBIOLOGICAL

SC injection

Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy

Pembrolizumab IVBIOLOGICAL

IV injection

Also known as: MK-3475, KEYTRUDA®, SCH 900475

Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy

PaclitaxelDRUG

IV injection

Also known as: Nov-Onxol, Onxol, Paclitaxel Novaplus, Taxol