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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
* 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
The Fourth Hospital of Hebei Medical University
Shijiazhuang, Hebei, China
Maximum Tolerated Dose (MTD)
MTD is defined as the highest dose level at which DLT is observed in ≤ 1/6 subjects at one single dose group
Time frame: Cycle 1 (21 days)
Recommended Phase 2 Dose (RP2D)
RP2D will be a dose either below or equal to MTD
Time frame: Cycle 1 (21 days)
Dose Limiting Toxicity (DLT)
DLT will be evaluated according to NCI-CTCAE V5.0 criteria
Time frame: Cycle 1 (21 days)
Objective response rate(ORR)
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)
Time frame: From first treatment date until disease progression or death, assessed every 6 weeks, up to approximately 36 months
Disease Control Rate (DCR)
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.
Time frame: From first treatment date until disease progression or death, assessed every 6 weeks, up to approximately 36 months
Progression free survival (PFS)
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.
Time frame: From first treatment date to disease progression or death, up to 36 months
2-year overall survival (OS) rate
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.
Time frame: From first treatment date to death from any cause, assessed up to 36 months
Incidence and severity of adverse events (AEs)
severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] Version \[v\] 5.0
Time frame: From first dose date through study completion, up to 36 months
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