Becotatug Vedotin in Combination With Immunotherapy and Multimodality Radiotherapy for Esophageal Squamous Cell Carcinoma in the Second-line or Later Setting

NCT07892833 | Recruiting Phase 2

• 1 other identifier: [ 2026 ] KY041
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single-arm, exploratory, single-center clinical study designed to evaluate the efficacy and safety of becotatug vedotin (MRG003) in combination with an investigator's choice of immune checkpoint inhibitor (ICI) plus multimodal radiotherapy in patients with advanced esophageal squamous cell carcinoma (ESCC) in the second-line or later setting. Treatment regimen for eligible subjects: Becotatug vedotin (MRG003): 2.0 mg/kg, administered intravenously on Day 1 of each 21-day cycle (Q3W), starting at least 30 minutes after completion of the ICI infusion. Immune checkpoint inhibitor: Investigator's choice, including but not limited to camrelizumab, tislelizumab, and pembrolizumab; Q3W, IV, Day 1, with infusion duration per the respective prescribing information. Multimodal radiotherapy: Initiated within the first 2 cycles of systemic therapy (no later than the end of Cycle 2), targeting the primary lesion and/or metastatic lesions. An individualized radiotherapy plan is delivered, using conventionally fractionated radiotherapy or stereotactic body radiotherapy (SBRT), at approximately 50-60 Gy in 25-30 fractions (or a biologically equivalent dose/fractionation schedule). Investigators may appropriately adjust the timing, dose, and fractionation. Whether the ICI is withheld during radiotherapy is left to the investigator's discretion based on the patient's clinical condition.

Conditions

ESCC

Keywords

Becotatug vedotin; ICIs; radiotherapy; ESCC

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  ORR is defined as the proportion of subjects achieving confirmed Complete Response (CR) or Partial Response (PR) as assessed by the investigator according to RECIST v1.1 and iRECIST criteria. ORR analysis will be based on the Full Analysis Set (FAS).

  up to 2years

Secondary Outcomes (5)

• Disease Control Rate

  up to 2years

• Progression-Free Survival

  up to 2years

• Overall survival

  up to 2years

• Duration of relief

  up to 2years

• Treatment Emergent Adverse Events (Safety and Tolerability）

  From the first dose of study treatment through 30 days after the last dose of study treatment (up to 2 years)

Study Arms (1)

Experimental

EXPERIMENTAL

Becotatug vedotin (MRG003): 2.0 mg/kg, D1,Q3W, starting at least 30 minutes after completion of the ICI infusion. Immune checkpoint inhibitor: Investigator's choice, including but not limited to camrelizumab, tislelizumab, and pembrolizumab; Q3W, IV, Day 1, with infusion duration per the respective prescribing information. Multimodal radiotherapy: Initiated within the first 2 cycles of systemic therapy (no later than the end of Cycle 2), targeting the primary lesion and/or metastatic lesions. An individualized radiotherapy plan is delivered, using conventionally fractionated radiotherapy or SBRT, at approximately 50-60 Gy in 25-30 fractions (or a biologically equivalent dose/fractionation schedule). Investigators may appropriately adjust the timing, dose, and fractionation. Whether the ICI is withheld during radiotherapy is left to the investigator's discretion based on the patient's clinical condition.

Drug: Becotatug vedotin (MRG003)

Interventions

Becotatug vedotin (MRG003) DRUG

1. Becotatug vedotin (MRG003): 2.0 mg/kg, D1,Q3W, starting at least 30 minutes after completion of the ICI infusion. 2. Immune checkpoint inhibitor: Investigator's choice, including but not limited to camrelizumab, tislelizumab, and pembrolizumab; Q3W, IV, Day 1, with infusion duration per the respective prescribing information. 3. Multimodal radiotherapy: Initiated within the first 2 cycles of systemic therapy (no later than the end of Cycle 2), targeting the primary lesion and/or metastatic lesions. An individualized radiotherapy plan is delivered, using conventionally fractionated radiotherapy or SBRT, at approximately 50-60 Gy in 25-30 fractions (or a biologically equivalent dose/fractionation schedule). Investigators may appropriately adjust the timing, dose, and fractionation. Whether the ICI is withheld during radiotherapy is left to the investigator's discretion based on the patient's clinical condition.

Also known as: Immune checkpoint inhibitor, radiotherapy

Experimental

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients voluntarily participated in the trial, fully informed consent, signed written informed consent, and had good compliance;
• Age of 18-80 years old (including the cut-off value), male or female;
• Recurrent/metastatic or unresectable advanced esophageal squamous cell carcinoma confirmed by pathology or histology;
• Failure of at least one previous standard therapy (including chemotherapy, PD-1 or PD-L1 inhibitors, etc.);
• At least one baseline extracranial measurable lesion, according to RECIST 1.1 criteria (≥10 mm in the greatest dimension on CT scan or ≥15 mm in the short dimension if the lesion is a lymph node), that had not received radiation therapy or had received previous local radiation therapy but was considered by the investigator to be reirradiated;
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-1;
• Expected survival time ≥12 weeks;
• The expression of epidermal growth factor receptor (EGFR) was confirmed by immunohistochemistry (IHC 1+,2+,3+);
• Previous antineoplastic treatment-related aes of NCI Common Terminology for Adverse Events version 5.0 (NCI CTCAE v5.0) ≤ grade 1 (except alopecia, non-clinically significant or asymptomatic laboratory abnormalities);
• The organ and bone marrow are sufficiently functional to meet the following requirements (within 14 days before starting study treatment) : 1) Blood routine examination: no blood transfusion, no use of granulocyte colony-stimulating factor \[G-CSF\], and no drug correction within 14 days before screening: hemoglobin \[HB\] ≥90g/L; Absolute neutrophil count (ANC) ≥1.5×109/L; Platelet (PLT) ≥75×109/L; 2) Blood biochemical tests should meet the following criteria (no albumin transfusion within 14 days before screening) : serum total bilirubin (BIL) ≤2×ULN (Gilbert's syndrome patients ≤3×ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5.0×ULN; Serum creatinine \[Cr\] ≤1.5×ULN or endogenous creatinine clearance ≥50ml/min (Cockcroft-Gault formula) Male: Cr clearance =((140-age)× body weight)/(72× blood Cr) Female: Cr clearance =((140-age)× weight)/(72× blood Cr) × 0.85 (Body weight: kg; blood Cr: mg/mL). 3) Coagulation function: international normalized ratio (INR) ≤2 or prothrombin time (PT) exceeding the upper limit of normal range ≤6 seconds;
• Female subjects of childbearing potential must take a urine or serum pregnancy test within 7 days before the first dose (if the urine pregnancy test result cannot be confirmed as negative, the serum pregnancy test should be taken, and the result is negative);
• If a female subject of childbearing potential has sex with an unsterilized male partner, the subject must be using an acceptable contraceptive method from the time of screening and must agree to continue using the method for 180 days after the last dose of study drug;
• If an unsterilized male subject has sex with a fertile female partner, the subject must use an effective method of contraception from the start of screening until 180 days after the last dose of medication; Discontinuation of contraception after this time point should be discussed with the investigator.
• Participants are willing and able to comply with the scheduled visits, treatment protocols, laboratory tests, and other requirements of the study.

You may not qualify if:

• The subjects had a malignancy other than esophageal squamous cell carcinoma within 5 years before enrollment. Note: Skin basal cell carcinoma, superficial bladder cancer, skin squamous cell carcinoma, or cervical cancer in situ were excluded. Or patients who had received curative treatment and had not relapsed within 5 years could participate in the trial;
• Known to be allergic to a drug or a drug component;
• Previous treatment interruption due to severe and/or life-threatening immune-related toxicity;
• NCI-CTCAE v5.0 grade of adverse events caused by previous antineoplastic therapy did not recover to ≤1 before enrollment (except alopecia or antineoplastic therapy-induced tolerable events according to investigator's opinion);
• Have received or are receiving any of the following: a) being treated with an immunosuppressive drug or systemic hormone for immunosuppression (at a dose of \>10 mg/ day of prednisone or equivalent) within 2 weeks before the first dose of the study drug; Use of inhaled or topical steroids and replacement adrenocortical hormones at a dose of more than 10 mg per day of prednisone or equivalent were allowed in the absence of active autoimmune disease. b) have received a live attenuated vaccine within 4 weeks before the first dose of study drug, or plan to receive a live or live attenuated vaccine during the study; c) major surgery or severe trauma within 4 weeks before the first dose of study drug;
• A history of immunodeficiency, including HIV positivity, other acquired or congenital immunodeficiency disorders, or organ or allogeneic bone marrow transplantation;
• Presence of uncontrolled cardiac symptoms or diseases, including but not limited to: heart failure above NYHA class Ⅱ, unstable angina pectoris, myocardial infarction within 1 year, and clinically significant supraventricular or ventricular arrhythmias without clinical intervention or poorly controlled after clinical intervention;
• Severe infection (CTCAE \> 2) occurred within 4 weeks before the first dose of study drug, such as severe pneumonia requiring hospitalization, bacteremia, infectious complications, etc. Patients who had active pulmonary inflammation on baseline chest imaging, had signs and symptoms of infection within 14 days before the first dose of the study drug, or required treatment with oral or intravenous antibiotics, except those who received prophylactic antibiotics;
• Patients with active pulmonary tuberculosis infection detected by medical history or CT examination, or with a history of active pulmonary tuberculosis infection within 1 year before enrollment, or with a history of active pulmonary tuberculosis infection more than 1 year before enrollment but without regular treatment;
• Presence of active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C (hepatitis C antibody positive and HCV RNA above the detection limit of the analytical method);
• Patients with clinically significant bleeding symptoms or clear bleeding tendency within 3 months before enrollment, such as daily cough/hemoptysis 2.5 mL or more lower gastrointestinal bleeding, esophageal and gastric varices with bleeding risk, bleeding gastric ulcer or angiitis;
• Arterial/venous thrombotic events occurred within 6 months before enrollment, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
• Pregnant or lactating women;
• According to the investigator's judgment, there are other factors that may lead to the forced termination of the study, such as other serious diseases (including mental diseases) requiring concomitant treatment, alcoholism, drug abuse, family or social factors, and factors that may affect the safety or compliance of the subjects;
• Is participating in another clinical study, unless it is an observational (noninterventional) clinical study or an interventional study follow-up.

Sponsors & Collaborators

• The First Affiliated Hospital of Bengbu Medical University: lead

Study Sites (1)

The First Affiliated Hospital of Bengbu Medical University

Bengbu, Anhui, 233000, China

RECRUITING

MeSH Terms

Interventions

Immune Checkpoint Inhibitors; Radiotherapy

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Therapeutics

Central Study Contacts

Hongwei Li, MD

CONTACT

+86-0552-3097010; hongweili@bbmu.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: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Becotatug vedotin in combination with immunotherapy and multimodality radiotherapy for esophageal squamous cell carcinoma in the second-line or later setting

Study Record Dates

• First Submitted: October 16, 2026
• First Posted: October 23, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): April 30, 2029
• Last Updated: October 23, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)