Esophageal Squamous Cell Carcinoma
Conditions
Keywords
Becotatug vedotin (EGFR-ADC）, LA-ESCC, Cisplatin and Concurrent Radiotherapy
Brief summary
This study is a prospective, single-arm, single-center Phase Ib clinical trial of Becotatug Vedotin in combination with cisplatin and concurrent radiotherapy for locally advanced esophageal squamous cell carcinoma. The primary objectives are to investigate the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and recommended Phase II dose (RP2D) of Becotatug Vedotin in combination with cisplatin and concurrent radiotherapy for locally advanced esophageal squamous cell carcinoma. The secondary objectives are to assess the efficacy and safety of this combination regimen.
Detailed description
This study is a prospective, open-label, single-center, dose-escalation Phase I clinical trial. During the dose-escalation phase, the classic "3+3" design will be used to guide dose escalation in order to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D). Eligible subjects who meet the inclusion and exclusion criteria will receive two cycles of Becotatug Vedotin in combination with cisplatin and concurrent radiotherapy, followed by subsequent systemic therapy per the investigator's discretion. The dose levels of Becotatug Vedotin are 1.5 mg/kg, 2.0 mg/kg, and 2.3 mg/kg (D1,IV,Q3W). Cisplatin is administered at a dose of 75 mg/m² (D1,IV,Q3W). The total radiotherapy dose is 50.4 Gy, delivered in 28 fractions of 1.8 Gy each. Dose-limiting toxicities (DLTs) will be observed during the treatment period until the completion of the entire concurrent chemoradiotherapy phase.
Interventions
DRUGBecotatug Vedotin Combined with Cisplatin and Concurrent Radiotherapy
* Becotatug Vedotin：1.5mg/kg 、2.0mg/kg、2.3mg/kg，d1;IV; Q3W * Cisplatin：75mg/m2，d1;IV; Q3W * Radiotherapy：50.4Gy/28f/1.8Gy
Sponsors
Hebei Medical University Fourth Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subjects who are able to understand and voluntarily sign informed consent forms (ICFs). * Male and female subjects at the age of ≥18 and ≤75 at the time of screening. * Histologically confirmed esophageal squamous cell carcinoma staged as cT2-T4a, N0-N+, M0-M1 (M1 limited to supraclavicular lymph node metastasis only). * Patients must have at least one measurable lesion as defined by RECIST version 1.1 criteria. * Patients who have not received any prior anti-tumor treatment for esophageal cancer. * ECOG score of 0 or 1. * Life expectancy ≥ 3 months. * Adequate organ function (no blood transfusion and no use of granulocyte colony-stimulating factor, or other hematopoietic stimulator support within 2 weeks before the first administration of the study drug) confirmed as evidenced by: 1. Absolute Neutrophil Count (ANC) ≥ 1.5×10\^9/L; 2. Hemoglobin (Hgb) ≥ 90 g/dl; 3. Platelets (Plt) ≥ 75×10\^9/L; 4. Bilirubin total ≤ 1.5 x ULN, or bilirubin direct \< ULN for patients with bilirubin total levels \>1.5 ULN; 5. AST/ALT ≤ 2.5 x ULN or ≤ 5.0 x ULN if liver metastases are present; 6. Serum creatinine \< 1.5 x ULN or creatinine clearance \> 50 mL/min (as calculated via Cockcroft-Gault formula based on the actual body weight of the subject ; * Female subjects must not be pregnant or breastfeeding. Female or male subjects of childbearing potential must agree to practice effective contraceptive measures throughout the study period and for 6 months after completion of study treatment.
Exclusion criteria
* Diagnosis of any other malignancy within the past 5 years (excluding carcinoma in situ, basal cell carcinoma, etc.). * Anyone allergic to any drug or any of its components in this regimen. * Patients with a prior history of surgery for esophageal squamous cell carcinoma. * Patients with a prior history of fistula caused by primary tumor infiltration. * Patients at high risk of gastrointestinal bleeding, esophageal fistula, or esophageal perforation. * Subjects with poor nutritional status, defined as BMI \< 18.5 kg/m² or PG-SGA score ≥ 9. * Patients with a diagnosis of pulmonary fibrosis or interstitial pneumonia within 28 days prior to enrollment. * Active infections such as HIV; active chronic HBV/HCV (e.g., HBV DNA ≥ 10⁴ copies/mL or ≥ 2000 IU/mL) requiring antiviral and hepatoprotective therapy before enrollment. Enrollment is allowed only when HBV DNA decreases to \< 10⁴ copies/mL or \< 2000 IU/mL, with continued antiviral therapy and regular monitoring of liver function and HBV DNA levels. * Presence of major cardiovascular disease, including any of the following conditions: 1. Congestive heart failure (defined as New York Heart Association \[NYHA\] Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, stent implantation, coronary artery bypass grafting, cerebrovascular accident (CVA), or hypertensive crisis within 6 months prior to enrollment. 2. History of clinically significant ventricular arrhythmias (e.g., sustained ventricular tachycardia, ventricular fibrillation, torsade de pointes). 3. Fridericia-corrected QT interval (QTcF) \> 450 msec in males or \> 470 msec in females. 4. History or family history of congenital long QT syndrome. 5. Arrhythmias requiring antiarrhythmic therapy (subjects with atrial fibrillation that has been controlled for more than 30 days prior to randomization may be enrolled). 6. History of deep vein thrombosis, pulmonary embolism, or any other serious thromboembolic event within 3 months prior to enrollment (thrombosis related to an implanted venous access port or catheter, or superficial venous thrombosis, is not considered "serious" thromboembolism). * Severe chronic diarrhea. * Severe psychiatric disorder. * Use of strong inhibitors or inducers of CYP3A4, CYP2C8, and UGT1A1. * Participation in another clinical trial within 4 weeks prior to enrollment. * Patients who, in the opinion of the investigator, are unsuitable for participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) | Cycle 1 (21 days) | MTD is defined as the highest dose level at which DLT is observed in ≤ 1/6 subjects at one single dose group |
| Recommended Phase 2 Dose (RP2D) | Cycle 1 (21 days) | RP2D will be a dose either below or equal to MTD |
| Dose Limiting Toxicity (DLT) | Cycle 1 (21 days) | DLT will be evaluated according to NCI-CTCAE V5.0 criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate（ORR） | From first treatment date until disease progression or death, assessed every 6 weeks, up to approximately 36 months | Objective response rate (ORR) is the proportion of subjects with the best overall response being CR or PR (assessed by investigator per RECIST v1.1) |
| Disease Control Rate (DCR) | From first treatment date until disease progression or death, assessed every 6 weeks, up to approximately 36 months | Disease Control Rate (DCR) is defined as the proportion of patients who achieve a best overall response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) according to RECIST 1.1 criteria, among the total number of evaluable patients. |
| Progression free survival (PFS) | From first treatment date to disease progression or death, up to 36 months | Progression-Free Survival (PFS) is defined as the time from randomization (or first dose of study treatment) to the first documented disease progression per RECIST 1.1 criteria, or death from any cause, whichever occurs first. |
| 2-year overall survival (OS) rate | From first treatment date to death from any cause, assessed up to 36 months | The 2-year overall survival (OS) rate is defined as the percentage of patients who remain alive at 2 years after the start of study treatment. |
| Incidence and severity of adverse events (AEs) | From first dose date through study completion, up to 36 months | severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] Version \[v\] 5.0 |
Countries
China
Contacts
CONTACTYunJie Cheng
Outcome results
None listed