Combination Immunotherapy of Adebrelimab With Apatinib and Tegafur for Immune Rechallenge Therapy in Esophageal Squamous Cell Carcinoma

NCT06339619 | Recruiting Phase 2

• 1 other identifier: SYSKY-2023-1262-02
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this single-arm study is to explore the efficacy and safety of Adebrelimab in combination with Apatinib and Tegafur for the treatment of locally advanced or metastatic esophageal squamous cell carcinoma that has failed first-line standard treatment with PD-1 inhibitors in combination with chemotherapy.

Conditions

Locally Advanced or Metastatic Esophageal Squamous Cell Carcinoma

Keywords

immunotherapy rechallenge; ESCC; Adebrelimab; Apatinib; PD-1 inhibitors; Tegafur; First-line treatment failure

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  ORR is determined as the percentage of patients who had complete response (CR) or partial response (PR) as best overall response per RECIST v1.1.

  6 months

Secondary Outcomes (3)

• Progression-free survival (PFS)

  6 months

• Overall survival (OS)

  12months

• ≥Grade 3 AEs

  6 months

Study Arms (1)

Adebrelimab+Apatinib+Tegafur

EXPERIMENTAL

Drug: Adebrelimab; Drug: Apatinib; Drug: Tegafur

Interventions

Adebrelimab DRUG

20mg/kg ivgtt D1 Q3W

Adebrelimab+Apatinib+Tegafur

Apatinib DRUG

250mg PO QD

Adebrelimab+Apatinib+Tegafur

Tegafur DRUG

dosing based on body surface area：BSA\<1.25m2,40mg; BSA=1.25～1.5m2,50mg; BSA\>1.5m2, 60mg，PO QD D1-21 Q3W

Adebrelimab+Apatinib+Tegafur

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old, both sexes.
• Esophageal squamous cell carcinoma confirmed by histology or cytology with locally advanced unresectable or distant metastasis (according to AJCC 8th edition).
• ECOG PS score of 0 \~ 1.
• Expected survival ≥3 months.
• Patients who have failed first-line immunotherapy combined with chemotherapy.
• At least one measurable or unmeasurable lesion according to RECIST V1.1 criteria (subjects with intracranial lesions alone were excluded from this study).
• Ability to swallow investigational drugs .
• The functional level of the organ must meet the following requirements. (1) ANC≥1.5×109/L; (2) PLT≥100×109/L; (3) Hb≥90 g/L; (4) Serum albumin ≥30 g/L; (5) TBIL≤1.5×ULN; ALT and AST≤2.5 x ULN; For patients with liver metastases, ALT and AST≤5×ULN; (6) Cr ≤1.5×ULN, or creatinine clearance ≥50mL/min as calculated by the Cockcroft-Gault formula; (7) Patients with urinary protein ≥++ should undergo further 24-hour quantitative detection of urinary protein, and the detection result should be\<1.0g.
• Within 7 days prior to enrollment, women of reproductive age must confirm a negative serum pregnancy test and consent to use effective contraception during the study drug use period and within 2 months after the last dose.
• Subjects voluntarily participate in the study after fully informed consent and sign the informed consent.

You may not qualify if:

• Have been diagnosed with other malignancies within 5 years, excluding: curable carcinoma in situ of the cervix, skin basal cell carcinoma or squamous cell carcinoma, or any other tumor that has been cured .
• Patients who had previously received treament of Adebrelimab, Apatinib or Tegafur.
• The following conditions occurred in the previous treatment history. (1)Used Chinese medicine anti-tumor treatment within 2 weeks; (2)Received other anti-tumor therapy within 4 weeks, including but not limited to chemotherapy, radiotherapy, and targeted therapy.
• Have not recovered from adverse events caused by prior antitumor therapy (i.e., ≤ grade 1 or at baseline).
• Subjects who have participated in or are participating in other clinical trials within 4 weeks.
• Received major surgery within 4 weeks or anticipated to undergo major surgery during the study period.
• Subject is currently using a CYP3A strong inhibitor or inducer, or has discontinued a strong inhibitor for less than 5 half-lives of the medication or discontinued a strong inducer for less than 5 half-lives of the medication or 14 days (whichever is longer) before dosing.
• Current need for treatment of central nervous system metastases or uncontrolled central nervous system metastases.
• Risk of severe bleeding or esophageal fistula.
• Clinically significant gastrointestinal abnormalities that may affect the intake, transport, or absorption of the drug.
• Those with active gastrointestinal ulcers, active gastrointestinal bleeding, or perforation.
• Within the 12 months prior to enrollment, individuals with any of the following conditions: myocardial infarction, coronary artery bypass grafting or peripheral artery bypass grafting surgery, congestive heart failure (III-IV graded by New York Heart Association), etc.; unstable angina within the 6 months prior to enrollment.
• Within the 12 months prior to enrollment, occurrence of thrombotic events or embolic events, such as cerebrovascular accidents (including transient ischemic attacks), deep vein thrombosis, pulmonary embolism, etc., or patients currently receiving thrombolytic or anticoagulant therapy such as warfarin, heparin, or other similar medications.
• Fridericia-corrected QT interval (QTcF)\>470 ms; history of congenital long QT syndrome; history of any clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes); left ventricular ejection fraction (LVEF) \<50%.
• Those with uncontrollable pleural effusion, pericardial effusion, pelvic effusion, or ascites requiring repeated drainage.

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead

Study Sites (1)

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Guangzhou, Guangdong, 510030, China

RECRUITING

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

apatinib; Tegafur

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)

Fluorouracil; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Minghui Wang

CONTACT

+86 13826276828; wmingh@mail.sysu.edu.cn

Study Design

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

Study Record Dates

• First Submitted: March 25, 2024
• First Posted: April 1, 2024
• Study Start: March 11, 2024
• Primary Completion: March 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: April 1, 2024

Record last verified: 2024-03

Locations

CN (1)