Study of Pembrolizumab (MK-3475) Versus Investigator's Choice of Chemotherapy for Participants With Advanced Esophageal/Esophagogastric Junction Carcinoma That Progressed After First-Line Therapy (MK-3475-181/KEYNOTE-181)-China Extension Study

NCT03933449 | Completed Phase 3 Results DMC FDA Drug

• 4 other identifiers: 3475-181 China Extension163145MK-3475-181KEYNOTE-181
• Study Type: interventional
• Target: 123
• Locations: 1 country
• Sites: 23

Brief Summary

In the China extension study, Chinese participants with advanced or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or Siewert type I adenocarcinoma of the esophagogastric junction (EGJ) that has progressed after first-line standard therapy will be randomized to receive either single agent pembrolizumab or the Investigator's choice of chemotherapy with paclitaxel, docetaxel, or irinotecan. The primary extension study hypothesis is that treatment with pembrolizumab will prolong overall survival (OS) as compared to treatment with chemotherapy.

Conditions

Esophageal Carcinoma; Esophagogastric Junction Carcinoma

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Overall Survival (OS) in All Participants

  OS was defined as the time from randomization to death due to any cause. Median OS for the first pembrolizumab course in all participants is presented.

  From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)

• Overall Survival (OS) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10)

  OS was defined as the time from randomization to death due to any cause. Median OS for the first pembrolizumab course in participants with a PD-L1 CPS ≥10 is presented.

  From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)

• Overall Survival (OS) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus

  OS was defined as the time from randomization to death due to any cause. Median OS for the first pembrolizumab course in participants with SCC of the esophagus is presented.

  From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)

Secondary Outcomes (8)

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

  From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)

• Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10)

  From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)

• Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus

  From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)

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

  From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)

• Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10)

  From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)

Study Arms (2)

Pembrolizumab

EXPERIMENTAL

Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to \~2 years). Participants who complete the first course of up to 35 administrations of pembrolizumab (\~2 years) but progress after discontinuation, may be eligible for a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 of each 3-week cycle for up to 17 cycles (up to \~1 year).

Biological: pembrolizumab

Chemotherapy

ACTIVE COMPARATOR

Participants receive Investigator's choice of chemotherapy: paclitaxel 80-100 mg/m\^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m\^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m\^2 IV on Day 1 of every 14-day (2-week) cycle (up to \~2 years).

Drug: paclitaxel; Drug: docetaxel; Drug: irinotecan

Interventions

pembrolizumab BIOLOGICAL

IV infusion

Also known as: KEYTRUDA®, MK-3475

Pembrolizumab

paclitaxel DRUG

IV infusion

Also known as: TAXOL®

Chemotherapy

docetaxel DRUG

IV infusion

Also known as: TAXOTERE®

Chemotherapy

irinotecan DRUG

IV infusion

Also known as: CAMPTOSAR®

Chemotherapy

Eligibility Criteria

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

You may qualify if:

• Histologically- or cytologically-confirmed diagnosis of adenocarcinoma or squamous cell carcinoma of the esophagus or Siewert type I adenocarcinoma of the EGJ
• Metastatic disease or locally advanced, unresectable disease
• Life expectancy of greater than 3 months
• Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
• Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
• Documented radiographic or clinical disease progression on no more or less than one previous line of standard therapy
• Can provide either a newly obtained or archival tumor tissue sample for intra-tumoral immune-related testing and for anti-programmed cell death (PD)-1
• Participants of reproductive potential must be willing to use adequate contraception for the course of the study through 120 days after the last dose of pembrolizumab or through 180 days after the last dose of paclitaxel, docetaxel or irinotecan
• Adequate organ function

You may not qualify if:

• 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 of the first dose of study medication
• Active autoimmune disease that has required systemic treatment in past 2 years
• Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication
• Known central nervous system (CNS) metastases and/or carcinomatous meningitis (includes past history or current metastasis)
• Has received prior anti-cancer monoclonal antibody (mAb), chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or not recovered from adverse events due to a previously administered agent
• Has had a severe hypersensitivity reaction to treatment with another mAb
• Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1), or anti-PD-L2 agent, or previously participated in Merck pembrolizumab (MK-3475) study
• Has a known additional malignancy that has progressed or required active treatment within the last 5 years with the exception of curatively treated basal cell and squamous cell carcinoma of the skin and/or curatively resected in-situ cervical and/or breast cancers, and in-situ or intra-mucosal pharyngeal cancer
• Received a live vaccine within 30 days of the first dose of study medication
• Known history of Human Immunodeficiency Virus (HIV) infection
• Known history of or is positive for hepatitis B (hepatitis B surface antigen reactive) or known active hepatitis C \[hepatitis C virus ribonucleic acid (RNA) or hepatitis C antibody is detected\]
• History of non-infectious pneumonitis that required steroids or current pneumonitis
• Active infection requiring systemic therapy
• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
• Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study starting with the screening visit through 120 days after the last dose of pembrolizumab or through 180 days after the last dose of paclitaxel, docetaxel or irinotecan

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (23)

Anhui Provincial Hospital ( Site 0708)

Hefei, Anhui, 230001, China

Location

The First Affiliated Hospital of Anhui Medical University ( Site 0707)

Hefei, Anhui, 230022, China

Location

Harbin Medical University Cancer Hospital ( Site 0714)

Harbin, Heilongjiang, 150081, China

Location

Wuhan Tongji Hospital ( Site 0724)

Wuhan, Hubei, 430030, China

Location

Hunan Cancer Hospital ( Site 0722)

Changsha, Hunan, 410013, China

Location

Jiangsu Cancer Hospital (Site 0704)

Nanjing, Jiangsu, 210000, China

Location

PLA Cancer Centre of Nanjing Bayi Hospital ( Site 0706)

Nanjing, Jiangsu, 210002, China

Location

Jilin Cancer Hospital ( Site 0718)

Changchun, Jilin, 130012, China

Location

The First Hospital Of Jilin University ( Site 0719)

Changchun, Jilin, 130021, China

Location

Zhejiang Cancer Hospital ( Site 0726)

Hangzhou, Zhejiang, 310022, China

Location

Beijing Cancer Hospital ( Site 0700)

Beijing, 100042, China

Location

Chinese PLA General Hospital (Site 0703)

Beijing, 100042, China

Location

Peking Union Medical College Hospital ( Site 0712)

Beijing, 100730, China

Location

Fujian Medical University Union Hospital ( Site 0721)

Fuzhou, 350001, China

Location

Fujian Province Cancer Hospital ( ( Site 0717)

Fuzhou, 350014, China

Location

The Second Affiliated Hospital of Zhejiang University School of Medicine ( Site 0705)

Hangzhou, 310009, China

Location

Sir Sun Sun Shaw Hosp, Zhejiang Univ,Oncology dept. ( Site 0720)

Hangzhou, 310016, China

Location

The Affiliated Hospital of Qingdao University ( Site 0709)

Qingdao, 266003, China

Location

Ruijin Hospital, Shanghai Jiaotong University ( Site 0701)

Shanghai, 200025, China

Location

Shanghai Chest Hospital ( Site 0727)

Shanghai, 200030, China

Location

Fudan University Shanghai Cancer Center ( Site 0723)

Shanghai, 200032, China

Location

Zhongshan Hospital affiliated to Fudan University ( Site 0715)

Shanghai, 200032, China

Location

Henan Cancer Hospital ( Site 0725)

Zhengzhou, 450008, China

Location

Related Publications (1)

• Cao Y, Qin S, Luo S, Li Z, Cheng Y, Fan Y, Sun Y, Yin X, Yuan X, Li W, Liu T, Hsu CH, Lin X, Kim SB, Kojima T, Zhang J, Lee SH, Bai Y, Muro K, Doi T, Bai C, Gu K, Pan HM, Bai L, Yang JW, Cui Y, Lu W, Chen J. Pembrolizumab versus chemotherapy for patients with esophageal squamous cell carcinoma enrolled in the randomized KEYNOTE-181 trial in Asia. ESMO Open. 2022 Feb;7(1):100341. doi: 10.1016/j.esmoop.2021.100341. Epub 2021 Dec 29.

  PMID: 34973513 RESULT

Related Links

• Merck Oncology Clinical Trial Information

MeSH Terms

Conditions

Esophageal Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; Paclitaxel; Docetaxel; Irinotecan

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Camptothecin; Alkaloids; Heterocyclic Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.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: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2019
• First Posted: May 1, 2019
• Study Start: December 29, 2016
• Primary Completion: February 13, 2019
• Study Completion: March 14, 2022
• Last Updated: March 29, 2023
• Results First Posted: February 26, 2020

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share

Locations

CN (23)