First-line Esophageal Carcinoma Study With Chemo vs. Chemo Plus Pembrolizumab (MK-3475-590/KEYNOTE-590)-China Extension Study

NCT03881111 | Withdrawn Phase 3 DMC FDA Drug

• 5 other identifiers: 3475-590 China Extension2017-000958-19173739MK-3475-590KEYNOTE-590
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 20

Brief Summary

The purpose of this Chinese extension study is to evaluate efficacy and safety of pembrolizumab plus cisplatin and 5-fluorouracil (5-FU) chemotherapy versus placebo plus cisplatin and 5-FU chemotherapy as first-line treatment in a Chinese cohort of participants with locally advanced or metastatic esophageal carcinoma. The primary efficacy hypotheses are that both progression-free survival (PFS), according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and determined by blinded independent central review, and overall survival (OS) are superior with pembrolizumab plus chemotherapy compared with placebo plus chemotherapy in all Chinese participants as well as Chinese participants whose tumors are programmed cell death-ligand 1 (PD-L1)-positive.

Conditions

Esophageal Neoplasms

Keywords

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

Outcome Measures

Primary Outcomes (4)

• Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 in all participants

  PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded independent central review or death due to any cause, whichever occurs first. For this analysis, PFS will be assessed in all participants.

  Up to 2 years

• PFS per RECIST Version 1.1 in PD-L1 biomarker-positive participants

  PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded independent central review or death due to any cause, whichever occurs first. For this analysis, PFS will be assessed in PD-L1 biomarker-positive participants.

  Up to 2 years

• Overall Survival (OS) in all participants

  OS is defined as the time from randomization to death due to any cause. For this analysis, OS will be assessed in all participants.

  Up to 2 years

• OS in PD-L1 biomarker-positive participants

  OS is defined as the time from randomization to death due to any cause. For this analysis, OS will be assessed in PD-L1 biomarker-positive participants.

  Up to 2 years

Secondary Outcomes (8)

• Objective Response Rate (ORR) per RECIST 1.1 in all participants

  Up to 2 years

• ORR per RECIST 1.1 in PD-L1 biomarker-positive participants

  Up to 2 years

• Duration of Response (DOR) per RECIST 1.1 in all participants

  Up to 2 years

• DOR per RECIST 1.1 in PD-L1 biomarker-positive participants

  Up to 2 years

• Number of participants with an adverse event (AE)

  Up to 27 months

Study Arms (2)

Pembrolizumab + Cisplatin + 5-FU

EXPERIMENTAL

Participants receive pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W), cisplatin 80 mg/m\^2 IV Q3W, and 5-FU 800 mg/m\^2/day continuous IV infusion on Days 1 to 5 (120 hours). All treatments will be administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.

Biological: Pembrolizumab; Drug: Cisplatin; Drug: 5-FU

Placebo + Cisplatin + 5-FU

PLACEBO COMPARATOR

Participants receive placebo to pembrolizumab (saline) IV Q3W, cisplatin 80 mg/m\^2 IV Q3W, and 5-FU 800 mg/m\^2/day continuous IV infusion on Days 1 to 5 (120 hours). All treatments will be administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.

Drug: Placebo; Drug: Cisplatin; Drug: 5-FU

Interventions

Pembrolizumab BIOLOGICAL

200 mg administered IV Q3W on Day 1 of each 3-week cycle, up to 35 administrations.

Also known as: MK-3475

Pembrolizumab + Cisplatin + 5-FU

Placebo DRUG

Placebo to pembrolizumab (saline) administered IV Q3W on Day 1 of each 3-week cycle, up to 35 administrations.

Placebo + Cisplatin + 5-FU

Cisplatin DRUG

80 mg/m\^2 administered IV Q3W on Day 1 of each 3-week cycle. Duration of cisplatin treatment will be capped at 6 doses.

Pembrolizumab + Cisplatin + 5-FU; Placebo + Cisplatin + 5-FU

5-FU DRUG

800 mg/m\^2/day (4000 mg/m\^2 total per cycle) administered as continuous IV infusion on Days 1 to 5 (120 hours) of each 3-week cycle, or per local standard for 5-FU administration.

Pembrolizumab + Cisplatin + 5-FU; Placebo + Cisplatin + 5-FU

Eligibility Criteria

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

You may qualify if:

• Has histologically- or cytologically-confirmed diagnosis of locally advanced unresectable or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the esophagogastric junction (EGJ)
• Has measurable disease per RECIST 1.1 as determined by the local site investigator/radiology assessment
• Eastern Cooperative Group (ECOG) performance status of 0 to 1
• Can provide either a newly obtained or archival tissue sample for PD-L1 by immunohistochemistry analysis
• Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to randomization and be willing to use an adequate method of contraception (e.g. abstinence, intrauterine device, diaphragm with spermicide, etc.) for the course of the study through 120 days after the last dose of study treatment and up to 180 days after last dose of cisplatin
• Male participants of childbearing potential must agree to use an adequate method of contraception (e.g. abstinence, vasectomy, male condom, etc.) starting with the first dose of study treatment through 120 days after the last dose of study treatment and up to 180 days after last dose of cisplatin, and refrain from donating sperm during this period
• Has adequate organ function

You may not qualify if:

• Has locally advanced esophageal carcinoma that is resectable or potentially curable with radiation therapy (as determined by local investigator)
• Has had previous therapy for advanced/metastatic adenocarcinoma or squamous cell cancer of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the EGJ
• Has had major surgery, open biopsy, or significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgery during the course of study treatment
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include early-stage cancers (carcinoma in situ or Stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, in situ breast cancer that has undergone potentially curative therapy, and in situ or intramucosal pharyngeal cancer
• Has known active central nervous system metastases and/or carcinomatous meningitis.
• Has an active autoimmune disease that has required systemic treatment in past 2 years
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment, or has a history of organ transplant, including allogeneic stem cell transplant
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis, or has an active infection requiring systemic therapy
• Is pregnant or 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 study medication and up to 180 days after last dose of cisplatin
• Has received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor or has previously participated in a pembrolizumab (MK-3475) clinical trial
• Has severe hypersensitivity (≥ Grade 3) to any study treatment (pembrolizumab, cisplatin, or 5-FU) and/or any of its excipients
• Has a known history of active tuberculosis (TB; Mycobacterium tuberculosis) or human immunodeficiency virus (HIV) infection
• Has known history of or is positive for hepatitis B or hepatitis C
• Has received a live vaccine within 30 days prior to the first dose of study treatment
• Has had radiotherapy within 14 days of randomization. Participants who received radiotherapy \>14 days prior to randomization must have completely recovered from any radiotherapy-related AEs/toxicities

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (20)

Anhui Provincial Hospital ( Site 0106)

Hefei, Anhui, 230036, China

Location

The First Affiliated Hospital of Anhui Medical University ( Site 0112)

Hefei, Anhui, 230088, China

Location

Peking Union Medical College Hospital ( Site 0123)

Beijing, Beijing Municipality, 100032, China

Location

The First Affiliated Hospital of Xiamen University ( Site 0119)

Xiamen, Fujian, 361000, China

Location

Guangdong General Hospital ( Site 0103)

Guangzhou, Guangdong, 510120, China

Location

The Affiliated Tumour Hospital of Harbin Medical University ( Site 0102)

Harbin, Heilongjiang, 150081, China

Location

Hunan Cancer Hospital ( Site 0105)

Changsha, Hunan, 410013, China

Location

PLA Cancer Centre of Nanjing Bayi Hospital ( Site 0110)

Nanjing, Jiangsu, 210002, China

Location

Jiangsu Cancer Hospital ( Site 0117)

Nanjing, Jiangsu, 210009, China

Location

Zhongda Hospital Southeast University ( Site 0125)

Nanjing, Jiangsu, 210009, China

Location

Jilin Cancer Hospital ( Site 0101)

Changchun, Jilin, 130012, China

Location

The First Affiliated Hospital of Xi an Jiaotong University ( Site 0120)

Xi'an, Shannxi, 710061, China

Location

Zhejiang Cancer Hospital ( Site 0116)

Hangzhou, Zhejiang, 310022, China

Location

Beijing Cancer Hospital ( Site 0100)

Beijing, 100142, China

Location

Fujian Provincial Cancer Hospital ( Site 0104)

Fuzhou, 350014, China

Location

Shanghai Chest Hospital ( Site 0111)

Shanghai, 200030, China

Location

Fudan University Shanghai Cancer Center ( Site 0108)

Shanghai, 200032, China

Location

Renji Hospital Shanghai Jiaotong University School of Medicine ( Site 0114)

Shanghai, 200127, China

Location

Tongji Medical College Huazhong University of Science and Technology ( Site 0109)

Wuhan, 430030, China

Location

Henan Cancer Hospital ( Site 0107)

Zhengzhou, 450008, China

Location

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

pembrolizumab; Cisplatin; Fluorouracil

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)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2019
• First Posted: March 19, 2019
• Study Start: January 21, 2019
• Primary Completion: May 11, 2021
• Study Completion: May 11, 2022
• Last Updated: February 11, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will share

Locations

CN (20)