An Umbrella-designed Prospective Multicenter Randomized Open-label Superiority Trial Evaluating Multi-biomarker-guided Precision Therapy for First-line Treatment of Advanced Esophageal Squamous Cell Carcinoma

NCT07709533 | Not Yet Recruiting Phase 2

• 1 other identifier: SL-B2025-677-01
• Study Type: interventional
• Target: 347
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, multicenter, randomized, open-label, umbrella superiority clinical trial for patients with advanced metastatic esophageal squamous cell carcinoma who have not received prior anti-tumor treatment. All eligible participants will be randomly assigned into two cohorts: Cohort A (standard treatment group) and Cohort B (biomarker-guided precision treatment group). Patients in Cohort A will receive first-line standard therapy consisting of TP chemotherapy plus PD-1 inhibitor. All patients in Cohort B will first complete three biomarker tests, then be divided into 4 sub-groups based on biomarker results to receive biomarker-directed additional treatment combined with the same standard backbone therapy. Participants with all negative biomarkers or failed biomarker testing will receive the identical standard treatment as Cohort A. The primary objective is to compare the survival benefit between biomarker-guided multi-strategy precision therapy and conventional standard first-line treatment.

Conditions

Valid MeSH Conditions

Keywords

Esophageal squamous cell carcinoma; TGF-β

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  Up to 2 Years

Secondary Outcomes (7)

• Objective Response Rate (ORR)

  Up to 2 Years

• Disease Control Rate (DCR)

  up to 2 years

• Duration of Response (DOR)

  up to 2 years

• Overall Survival (OS)

  up to 2 years

• quality of life score

  up to 2 years

Other Outcomes (3)

• Correlation analysis between TGFβ and Incidence of treatment response

  up to 2 years

• Correlation analysis between Metabolite Score and Incidence of treatment response

  up to 2 years

• Correlation analysis between blood Lactobacillus qPCR levels and Incidence of treatment response

  up to 2 years

Study Arms (2)

Conventional Therapy

ACTIVE COMPARATOR

Participants in this arm will receive standard first-line treatment for advanced esophageal squamous cell carcinoma, consisting of TP chemotherapy plus a PD-1 inhibitor. TP regimen refers to Nab-Paclitaxel combined with cisplatin.

Drug: Paclitaxel + Cisplatin (TP regimen) plus PD-1 inhibitor

Experimental Arm

EXPERIMENTAL

Subgroup B1 (TGF-β-guided Intervention): Patients with positive plasma TGF-β levels detected by ELISA; they will receive Retlirafusp alfa combined with chemo-immunotherapy backbone. Subgroup B2 (Metabolite-guided Intervention): Patients who do not meet the criteria for Subgroup B1 and have positive plasma metabolite predictive score; they will receive indole-3-carbinol plus fermented black garlic extract combined with chemo-immunotherapy backbone. Subgroup B3 (Lactobacillus-guided Intervention): Patients who do not meet the criteria for Subgroup B1 or B2 and have positive blood Lactobacillus levels measured by qPCR; they will receive Lactobacillus rhamnosus combined with chemo-immunotherapy backbone. Subgroup B4 (Screening Failure Subgroup): Patients with negative results for all three biomarkers due to technical issues; they will receive the same conventional treatment as Cohort A.

Drug: Retlirafusp alfa / Indole-3-carbinol + Black garlic fermentation extract / Lactobacillus rhamnosus / Placebo + Paclitaxel + Cisplatin (TP regimen) plus PD-1 inhibitor

Interventions

Paclitaxel + Cisplatin (TP regimen) plus PD-1 inhibitor DRUG

Paclitaxel + Cisplatin (TP regimen) plus PD-1 inhibitor

Conventional Therapy

Retlirafusp alfa / Indole-3-carbinol + Black garlic fermentation extract / Lactobacillus rhamnosus / Placebo + Paclitaxel + Cisplatin (TP regimen) plus PD-1 inhibitor DRUG

Group B1 (TGF-guided intervention, n=73): Plasma TGF-B ELISA levels positive, combined with Retlirafusp alfa on top of chemo-immunotherapy backbone; Group B2 (metabolite-guided intervention, n=73): Did not meet TGF-β positivity, combined with indole-3-carbinol and black garlic fermentation extract on top of chemo-immunotherapy backbone; Group B3 (Lactobacillus-guided intervention, n=73): Those who don't meet B1 or B2 criteria but have positive blood Lactobacillus qPCR levels, combined with Lactobacillus rhamnosus on top of chemo-immunotherapy backbone; Group B4 (Screening failed group, n=55): All three biomarker tests are negative or testing failed due to technical reasons, receive the same conventional treatment as cohort A

Experimental Arm

Eligibility Criteria

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

You may qualify if:

• Aged between 18 and 75 years (calculated on the date of signing the informed consent form);
• Patients with metastatic esophageal squamous cell carcinoma (ESCC) confirmed by histopathology or cytology;
• Treatment-naïve patients with no prior anti-tumor therapy;
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1, with an expected survival of more than 3 months;
• Judged by the investigator to be suitable for first-line chemotherapy;
• Presence of at least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1);
• Women of childbearing potential must agree to use effective contraception (e.g., intrauterine device, oral contraceptives, condoms) throughout the study period and for 6 months after the end of study treatment; they must have a negative serum or urine pregnancy test within 7 days prior to enrollment and shall not be breastfeeding. Male patients must agree to use effective contraception throughout the study period and for 6 months after the end of study treatment.
• Version: 1.0, Version Date: March 18, 2026
• Voluntarily participate in this study and provide written informed consent.

You may not qualify if:

• Brain metastases with symptoms or symptom control duration less than 2 months;
• History of or concurrent other malignant tumors within the past 3 years (excluding cured basal cell carcinoma of the skin and carcinoma in situ of the cervix);
• Insufficient bone marrow hematopoietic function (without blood transfusion within 14 days):
• Absolute Neutrophil Count (ANC) \< 1.5 × 10⁹/L;
• Platelet count \< 100 × 10⁹/L;
• Hemoglobin \< 90 g/L.
• Hepatic abnormalities:
• Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) or Alkaline Phosphatase (ALP) \> 2.5 × Upper Limit of Normal (ULN) in patients without liver metastases; ALT, AST or ALP \> 5 × ULN in patients with liver metastases;
• Serum total bilirubin \> 1.5 × ULN (\> 3 × ULN for patients with Gilbert's syndrome);
• Decompensated liver cirrhosis (Child-Pugh liver function grade B or C);
• Positive Hepatitis B Surface Antigen (HBsAg) with Hepatitis B Virus (HBV) DNA load ≥ 2000 IU/mL. Patients with positive HBsAg and HBV DNA load \< 2000 IU/mL must receive anti-HBV therapy for at least 2 weeks prior to the first study drug administration;
• Positive Hepatitis C Virus (HCV) antibody with detectable HCV RNA.
• Renal abnormalities:
• Serum creatinine \> 1.5 × ULN or estimated creatinine clearance \< 60 mL/min calculated by the Cockcroft-Gault formula;
• Urinalysis showing urine protein ≥ ++, confirmed with 24-hour urinary protein quantification \> 1.0 g;

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sub-i

Guangdong, GUANGZHOU, 510000, China

Location

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

Paclitaxel; Cisplatin; TP protocol; indole-3-carbinol

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)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Central Study Contacts

XU ruihua Xuruihua

CONTACT

020-87342479; luohy@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Academician

Study Record Dates

• First Submitted: July 6, 2026
• First Posted: July 16, 2026
• Study Start: July 7, 2026
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): June 30, 2029
• Last Updated: July 16, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: The data can be shared when the study is finished and ready for publication.
• Access Criteria: PI

Locations

CN (1)