Afatinib Plus Toripalimab in Previously Treated ESCC With EGFR Overexpression or EGFR Amplification

Phase 2 Study of Afatinib Plus Toripalimab in Previously Treated Recurrent or Metastasic Esophageal Squamous Cell Carcinoma With EGFR Overexpression or EGFR Amplification

This is a phase 2 trial investigating the effect and safety of afatinib plus toripalimab in previously treated recurrent or metastasic esophageal squamous cell carcinoma with EGFR overexpression or EGFR amplification.

Study Overview

• Status: Not yet recruiting
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Afatinib; Drug: Toripalimab

• Study Type: Interventional
• Enrollment (Anticipated): 43
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhihao Lu, Professor; Phone Number: 86-10-88196561; Email: 13810549767@126.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Peking University Cancer Hospital and Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Having signed informed consent.
2. Age 18 to 70 years old.
3. Histologically confirmed esophageal squamous carcinoma
4. Immunohistochemistry confirmed EGFR(3+) or EGFR-FISH-amplification or next generation sequencing confirmed EGFR-amplification.
5. Computed tomography (CT) or magnetic resonance imaging (MRI) confirmed unresectable metastasic or recurrent ESCC.
6. Refractory or intolerant to at least one regimen.
7. Measurable disease according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria(diameter of the lesion should be more than 10mm by spiral CT or MRI, more than 20mm by common CT, the date of image should be less than 21 days before enrollment)
8. Life expectancy of ≥3 month
9. Eastern Cooperative Oncology Group (ECOG) 0-2
10. WBC>3,000/mm3, absolute neutrophil count ≥1500/mm3, platelet>100,000/mm3, Hb>9g/dl，Bilirubin level < 1.5 times ULN，Serum creatinine <1.5 times ULN，ALT and AST<2.5 times ULN ，AKP < 2.5 times ULN ，(≤5 times ULN in patients with liver metastases)(within 7 days before enrollment)
11. No sever complication, such as active gastrointestinal bleeding, perforation, jaundice, obstruction, non-cancerous fever>38℃.
12. Good compliance

Exclusion Criteria:

1. Currently receiving other effective regimens.
2. Previous anticipate other clinical trial within 4 weeks before entering this study.
3. No measurable lesions, eg. pleural fluid and ascites.
4. With other malignancy within 5 year, except non-melanoma skin cancer and cervical carcinoma in situ.
5. Heart failure or other sever organ dysfunction, eg. coronary artery disease, myocardial infarction within the last 6 months.
6. Mentally abnormal or disable cognition,including central nervous system (CNS) metastasis.
7. HIV infection, active hepatitis B or hepatitis C.
8. Unstable systemic diseases such as poorly controlled diabetes.
9. Interstitial lung disease, such as interstitial pneumonia, pulmonary fibrosis, or evidence of interstitial lung disease showed in X-ray/CT.
10. Keratitis, ulcerative keratitis or severe dry eye syndrome. Known hypersensitivity to study drug.
11. Pregnancy or lactation period.
12. Active severe infection within 14 days
13. Contraindications of afatinib.
14. Pregnancy (determined by serum β-chorionic gonadotropin test) or breast-feeding
15. Gastrointestinal perforation and/or fistula occurred within 3 months before enrollment
16. Patients with active autoimmune disease or stable disease with high risk of recurrence
17. Use corticosteroids (dose of prednisone or similar drugs> 10mg/day) or other immunosuppressive agents within 14 days before enrollment
18. Live vaccine was injected within 4 weeks before enrollment
19. Previously received treatment with EFFR-TKI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Afatinib plus toripalimab	Drug: Afatinib; Afatinib is orally administered at 40mg Qd of each 21 day cycle.; Drug: Toripalimab; Toripalimab is given by intravenous infusion at 200mg d1 of each 21 day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	Percentage of patients who achieve partial response (PR) or complete response (CR) based on Response Evaluation Criteria In Solid Tumors (RECIST).	From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Related Adverse Events	Number of adverse events.	Until 30 days after the last treatment
Duration of response	Measure of time from first response to disease progression or death	Up to 2 years
Disease control rate	Percentage of patients who achieve partial response (PR) or complete response (CR) or stable disease (SD) based on Response Evaluation Criteria In Solid Tumors (RECIST).	From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months.
Progression free survival	Measure of time from study treatment to disease progression or death.	Up to 2 years
Overall survival	Measure of time from study treatment to patient's death or lost to follow-up.	Up to 2 years

Collaborators and Investigators

• Sponsor: Peking University

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): July 1, 2021
• Primary Completion (ANTICIPATED): October 1, 2022
• Study Completion (ANTICIPATED): May 1, 2023

Study Registration Dates

• First Submitted: May 6, 2021
• First Submitted That Met QC Criteria: May 6, 2021
• First Posted (ACTUAL): May 11, 2021

Study Record Updates

• Last Update Posted (ACTUAL): July 13, 2021
• Last Update Submitted That Met QC Criteria: July 11, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: toripalimab; afatinib; EGFR Overexpression; EGFR Amplification
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Afatinib
• Other Study ID Numbers: ESCC-AT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No