Combination immunotherapy for advanced esophageal cancer

Phase II Clinical Study of Adebrelimab Combined With Apatinib and Tegafur in the Treatment of Locally Advanced or Metastatic Esophageal Squamous Cell Carcinoma That Failed First-line Immunotherapy Combined With Chemotherapy

This study is testing a new combination of treatments for patients with advanced esophageal cancer who haven't responded to previous therapies to see if it can help them.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 32 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University (Academic / other)
• Drugs / interventions: Adebrelimab, Apatinib, chemotherapy, immunotherapy, radiation
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06339619 on ClinicalTrials.gov

What this trial studies

This single-arm phase II study aims to evaluate the efficacy and safety of Adebrelimab combined with Apatinib and Tegafur in patients with locally advanced or metastatic esophageal squamous cell carcinoma who have not responded to first-line treatment with PD-1 inhibitors and chemotherapy. The study will enroll 32 patients who will receive the treatment regimen over 21-day cycles until disease progression or intolerable toxicity occurs. The goal is to explore new therapeutic options for patients facing limited treatment choices after standard therapies fail.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with locally advanced or metastatic esophageal squamous cell carcinoma who have failed first-line immunotherapy combined with chemotherapy.

Not a fit: Patients with intracranial lesions or those who have not failed first-line treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with advanced esophageal cancer who have exhausted standard therapies.

How similar studies have performed: Previous studies have shown some therapeutic advantages of combining PD-1 inhibitors with anti-angiogenic drugs, but this specific combination is being explored for the first time in this context.

Eligibility criteria

Inclusion Criteria:

1. 18-75 years old, both sexes.
2. Esophageal squamous cell carcinoma confirmed by histology or cytology with locally advanced unresectable or distant metastasis (according to AJCC 8th edition).
3. ECOG PS score of 0 \~ 1.
4. Expected survival ≥3 months.
5. Patients who have failed first-line immunotherapy combined with chemotherapy.
6. At least one measurable or unmeasurable lesion according to RECIST V1.1 criteria (subjects with intracranial lesions alone were excluded from this study).
7. Ability to swallow investigational drugs .
8. 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.
9. 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.
10. Subjects voluntarily participate in the study after fully informed consent and sign the informed consent.

Exclusion Criteria:

1. 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 .
2. Patients who had previously received treament of Adebrelimab, Apatinib or Tegafur.
3. 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.
4. Have not recovered from adverse events caused by prior antitumor therapy (i.e., ≤ grade 1 or at baseline).
5. Subjects who have participated in or are participating in other clinical trials within 4 weeks.
6. Received major surgery within 4 weeks or anticipated to undergo major surgery during the study period.
7. 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.
8. Current need for treatment of central nervous system metastases or uncontrolled central nervous system metastases.
9. Risk of severe bleeding or esophageal fistula.
10. Clinically significant gastrointestinal abnormalities that may affect the intake, transport, or absorption of the drug.
11. Those with active gastrointestinal ulcers, active gastrointestinal bleeding, or perforation.
12. 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.
13. 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.
14. 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%.
15. Those with uncontrollable pleural effusion, pericardial effusion, pelvic effusion, or ascites requiring repeated drainage.
16. Past or current interstitial lung disease or immune-related pneumonia; currently suffering from drug-induced pneumonia, radiation pneumonia requiring steroid therapy, or clinically symptomatic active pneumonia, or other moderate to severe pulmonary diseases severely affecting lung function.
17. Active infection during screening, or unexplained fever\>38.5°C within 2 weeks prior to randomization.
18. Active hepatitis B or hepatitis C.
19. Received live vaccines within 4 weeks prior toenrollment and/or planned to receive live vaccines after enrollment.
20. Those with congenital or acquired immunodeficiency (such as HIV-infected individuals).
21. History of organ transplantation or allogeneic bone marrow transplantation.
22. Individuals deemed by the investigator to have other serious acute or chronic illnesses unsuitable for participation in the clinical trial.

Where this trial is running

Guangzhou, Guangdong

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Minghui Wang

Conditions Locally Advanced or Metastatic Esophageal Squamous Cell Carcinoma; immunotherapy rechallenge; ESCC; Adebrelimab; Apatinib; PD-1 inhibitors; Tegafur; First-line treatment failure