Adjuvant Pembrolizumab for Patients With Locally Advanced Esophageal Squamous Cell Carcinoma at High Risk of Recurrence

NCT03322267 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 201708042MIPD
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, participants with histologically diagnosed locally advanced esophageal squamous cell carcinoma who have received preoperative cisplatin-based chemoradiotherapy followed by surgery harbouring high risk of tumor recurrence will receive adjuvant cisplatin-based chemoradiotherapy followed by pembrolizumab. The primary study hypothesis is that adjuvant pembrolizumab will improve the 1-year recurrence-free survival rate compared to historical control.

Conditions

Esophageal Squamous Cell Carcinoma

Keywords

Adjuvant pembrolizumab; Chemoradiotherapy

Outcome Measures

Primary Outcomes (1)

• 1-year Relapse-free Survival Rate

  From enrollment to relapse or death

  up to 21.6 months

Secondary Outcomes (5)

• The Median RFS

  21.6 months

• The Median Overall Survival (OS)

  21.6 months

• The 3-year RFS Rate

  3 years

• The 3-year OS Rate.

  3 years

• Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)

  3 years

Other Outcomes (2)

• Tissue-based Biomarkers

  3 years

• Blood-based Biomarkers

  3 years

Study Arms (1)

Pembrolizumab

EXPERIMENTAL

Adjuvant cisplatin-chemoradiotherapy followed by pembrolizumab

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Cisplatin (30 mg/m2, QW, 2 cycles) and radiotherapy (18-26 Gy/10-13 fractions) as adjuvant chemoradiotherapy, followed by pembrolizumab (200mg, Q3W, 18 cycles)

Also known as: cisplatin, radiotherapy

Pembrolizumab

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• Be ≥ 20 years of age on day of signing informed consent.
• Be a diagnosed by pathology or cytology with a locally advanced ESCC, which is clinically stage according to the TNM system of the American Joint Committee on Cancer (AJCC) Cancer Staging System (7th edition), fulfilling one of the following criteria as determined by endoscopic ultrasound, computed tomography, bronchoscopy and positron emission tomography:
• T3, N0, M0;
• T4a, N0, M0;
• T1-4a, N1-3, M0.
• Have been treated with preoperative cisplatin-based CRT followed by esophagectomy with lymph node dissection for the locally advanced ESCC (defined by above criteria).
• Have a performance status of 0 or 1 on the ECOG Performance Scale.
• Exhibit at least one risk factor of tumor recurrence in the post-CRT surgical tissues:
• Close (≤1mm) or involved margin;
• Residual tumor cells in lymph nodes with extranodal invasion.
• ypN2 or ypN3.
• Adequate hemogram and organ function:
• Absolute neutrophil count ≥1,500 /mcL; platelets ≥100,000 / mcL; hemoglobin ≥9 g/dL without transfusion or EPO dependency (within 7 days of assessment)
• Serum creatinine ≤1.5 X upper limit of normal or measured or calculated creatinine clearance ≥60 mL/min; serum total bilirubin ≤ 1.5 X ULN; AST and ALT ≤ 2.5 X ULN; albumin \>2.5 mg/dL; international normalized ratio or prothrombin time and activated partial thromboplastin time ≤1.5 X ULN unless subject is receiving anticoagulant therapy

You may not qualify if:

• Is diagnosed with adenocarcinoma of esophagus or gastroesophageal junction.
• Has synchronously diagnosed with a squamous cell carcinoma of aero-digestive way, other than esophageal cancer.
• Has prior malignancy, except for: (a) adequately treated basal cell or squamous cell skin cancer; (b) in-situ cervical cancer; (c) previously diagnosed malignancy which have been adequately treated and shown no evidence of recurrence for more than 5 years.
• 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 of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

Sponsors & Collaborators

• National Taiwan University Hospital: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Related Publications (1)

• Guo JC, Huang TC, Kuo HY, Lin CC, Hsu FM, Cheng JC, Huang YL, Hsieh MS, Huang PM, Lee JM, Wu SL, Hsu CH. Adjuvant chemoradiotherapy plus pembrolizumab for locally advanced esophageal squamous cell carcinoma with high risk of recurrence following neoadjuvant chemoradiotherapy: a single-arm phase II study. Cancer Immunol Immunother. 2024 Sep 9;73(11):230. doi: 10.1007/s00262-024-03826-y.

  PMID: 39249605 DERIVED

Related Links

• Published results

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

pembrolizumab; Cisplatin; Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Therapeutics

Results Point of Contact

• Title: Dr Chih-Hung Hsu
• Organization: National Taiwan University Hospital

chihhunghsu@ntu.edu.tw

+886-23123456

Study Officials

• Chih-Hung Hsu, MD, PhD

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Adjuvant cisplatin-chemoradiotherapy followed by pembrolizumab

Study Record Dates

• First Submitted: October 16, 2017
• First Posted: October 26, 2017
• Study Start: October 27, 2018
• Primary Completion: January 31, 2024
• Study Completion: January 30, 2026
• Last Updated: March 6, 2026
• Results First Posted: December 19, 2024

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)