Prospective, Open-label, Multi-cohort Study of Becotatug Vedotin With Tislelizumab and Chemotherapy in Esophageal Squamous Cell Carcinoma - Phase 2

NCT07531979 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: PROGRESS
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 1

Brief Summary

Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor worldwide, with particularly high incidence in East Asian regions such as China, and is associated with poor patient prognosis. In recent years, immune checkpoint inhibitors (e.g., anti-PD-1/PD-L1 antibodies) combined with chemotherapy have become the standard first-line treatment for advanced ESCC. Multiple randomized controlled trials have confirmed that this combination significantly improves patient survival compared to chemotherapy alone. However, a subset of patients still exhibit poor response or develop resistance to the immunotherapy-chemotherapy regimen, necessitating the exploration of novel combination strategies to further enhance efficacy. The epidermal growth factor receptor (EGFR) is frequently overexpressed in ESCC and is associated with tumor proliferation, metastasis, and poor prognosis, making it an important therapeutic target. Antibody-drug conjugates (ADCs) targeting EGFR achieve precise tumor killing by conjugating an anti-EGFR antibody to a potent cytotoxic payload. Preclinical studies have demonstrated significant antitumor activity of EGFR ADCs in ESCC models. Mechanistically, anti-EGFR therapy and immune checkpoint inhibitor therapy may exert synergistic effects through several avenues: enhancing tumor antigen presentation, remodeling the tumor microenvironment, and modulating PD-L1 expression. Therefore, this triple combination strategy holds promise for overcoming the limitations of monotherapies and providing a new treatment option for patients with ESCC.

Conditions

ESCC; Tislelizumab; Chemotherapy; Becotatug Vedotin; EGFR ADC; PD-1 Inhibitor

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  The Overall Response Rate (ORR): is defined as the proportion of patients who achieved complete response (CR) or partial response (PR) as the best response during the treatment. evaluated by the investigator according to RECIST 1.1 criteria.

  up to 24 months

Secondary Outcomes (9)

• Arm A：Disease Control Rate (DCR)

  up to 24 months

• Arm B: Pathological Complete Response (pCR) rate

  up to 24 months

• Arm A: Progression Free Survival (PFS)

  up to 24 months

• Arm A: Overall Survival (OS)

  up to 48 months

• Arm A: Adverse Events (AE)

  up to 36 months

Study Arms (2)

Arm A: first-line treatment for advanced cohort

EXPERIMENTAL

Tislelizumab + Becotatug Vedotin + cisplatin (for up to 6 cycles), followed by tislelizumab monotherapy as maintenance treatment (for up to 2 years).

Drug: Tislelizumab; Drug: Becotatug Vedotin; Drug: Cisplatin

Arm B: preoperative neoadjuvant therapy cohort

EXPERIMENTAL

Tislelizumab + Becotatug Vedotin + cisplatin (for 3 cycles), followed by tislelizumab monotherapy as adjuvant treatment after surgery (for up to 1 year)

Drug: Tislelizumab; Drug: Becotatug Vedotin; Drug: Cisplatin

Interventions

Tislelizumab DRUG

Tislelizumab 200mg IV Q3W + Followed by maintenance treatment for 2 year (Tislelizumab 200 mg IV Q3W for 6 cycles and Tislelizumab 200 mg Q3W for 28 cycles)

Arm A: first-line treatment for advanced cohort

Becotatug Vedotin DRUG

2mg/kg or 2.3mg/kg，D1，Q3W, 6 cycles

Arm A: first-line treatment for advanced cohort

Cisplatin DRUG

60mg/㎡, D1, Q3W, 6 cycles

Arm A: first-line treatment for advanced cohort

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years.
• Male or non-pregnant, non-lactating female.
• ECOG performance status of 0 or 1, with no deterioration within 7 days.
• Histologically confirmed locally advanced or metastatic esophageal squamous cell carcinoma.
• No prior systemic therapy for ESCC. Patients who have received neoadjuvant or adjuvant therapy must have experienced disease progression or recurrence more than 6 months after completion of that treatment.
• Patients with metastatic disease must have at least one measurable lesion per RECIST 1.1 criteria; patients with disease after neoadjuvant therapy must have an evaluable lesion.
• Adequate organ and bone marrow function, as demonstrated by the following laboratory values:
• Hemoglobin (HGB) ≥ 90 g/L.
• Absolute neutrophil count (NEUT) ≥ 1.5 × 10⁹/L.
• Platelet count (PLT) ≥ 80 × 10⁹/L.
• Total bilirubin (TBIL) ≤ 1.5 × the upper limit of normal (ULN).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; for patients with liver metastases, ALT and AST ≤ 5 × ULN.
• Creatinine clearance ≥ 50 mL/min (calculated by the Cockcroft-Gault formula).
• Urine protein \< (++) or 24-hour urinary protein \< 1.0 g.
• Normal coagulation function and no active bleeding:

You may not qualify if:

• Patients meeting any of the following criteria at screening will be excluded from the study:
• Prior treatment with any anti-EGFR monoclonal antibody, or with anti-PD-1/PD-L1 antibody, anti-PD-L2 antibody, anti-CD137 antibody, CTLA-4 antibody, or any other drug/antibody targeting T-cell co-stimulation or checkpoint pathways.
• Administration of a live vaccine within 4 weeks prior to enrollment or anticipated during the study period.
• Active autoimmune disease or a history of autoimmune disease within 4 weeks prior to enrollment.
• Prior allogeneic bone marrow transplantation or solid organ transplant.
• Uncontrolled hypertension at enrollment, defined as: systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 90 mmHg.
• Any disease or condition affecting drug absorption at enrollment.
• Clinically significant cardiovascular disease, including but not limited to: acute myocardial infarction within 6 months prior to enrollment; severe/unstable angina or coronary artery bypass grafting; congestive heart failure \> New York Heart Association (NYHA) Class 2; ventricular arrhythmias requiring medication; left ventricular ejection fraction (LVEF) \< 50%.
• Active or uncontrolled severe infection (≥ CTCAE v5.0 Grade 2 infection).
• Known HIV infection. Known clinically significant liver disease, including viral hepatitis \[known hepatitis B virus (HBV) carriers must be excluded if they have active HBV infection, i.e., HBV DNA positive (\>1×10⁴ copies/mL or \>2000 IU/mL); known hepatitis C virus (HCV) infection with HCV RNA positive (\>1×10³ copies/mL)\].
• Any other disease, clinically significant metabolic abnormality, physical examination finding, or laboratory abnormality that, in the investigator's judgment, reasonably suggests the presence of a disease or condition that contraindicates the use of the investigational drug (e.g., a condition associated with seizures requiring treatment), would affect the interpretation of study results, or would place the patient at high risk.
• Patients deemed by the investigator to be unsuitable for participation in this study.

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (1)

Tianjin Medical University Cancer Institute and Hospital

Tianjin, China

Location

MeSH Terms

Interventions

tislelizumab; Cisplatin

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study comprises two cohorts: Cohort 1 consists of patients with treatment-naïve advanced or metastatic ESCC, and Cohort 2 consists of patients with locally advanced ESCC.

Study Record Dates

• First Submitted: March 16, 2026
• First Posted: April 15, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): December 31, 2029
• Last Updated: April 15, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)