This study aims to evaluate the efficacy and safety of neoadjuvant sacituzumab tirumotecan (SKB264/MK-2870) combined with toripalimab in patients with locally advanced, resectable esophageal squamous cell carcinoma (ESCC). Eligible participants will receive 3 cycles of neoadjuvant treatment, followed by radical surgery. The primary endpoint is the pathologic complete response (pCR) rate.
This is a prospective, single-arm, phase II study planned to enroll 33 participants with histologically or cytologically confirmed locally advanced esophageal squamous cell carcinoma (clinical stage cT1-2N+M0 or T3-4N0-3M0, stage II-IVA) who are candidates for surgery and require neoadjuvant therapy. After screening within 28 days before the first dose, eligible participants will receive sacituzumab tirumotecan 4 mg/kg intravenously once every 2 weeks on day 1 for 3 cycles, in combination with toripalimab 3 mg/kg intravenously once every 2 weeks on day 1 for 3 cycles. When administered on the same day, toripalimab is infused first, followed by sacituzumab tirumotecan after an interval of at least 30 minutes. Tumor response will be assessed based on RECIST v1.1, and radical surgery will be performed within 28 days after completion of neoadjuvant therapy. Tumor assessments will be performed every 3 months for the first 2 years after surgery and every 6 months thereafter until radiologically confirmed disease progression. Survival follow-up will be conducted every 3 to 6 months by telephone. Safety will be assessed according to NCI CTCAE v5.0.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
33
4 mg/kg administered intravenously on day 1 of each 14-day cycle for 3 cycles. Premedication is required before each infusion to prevent infusion-related reactions.
3 mg/kg administered intravenously on day 1 of each 14-day cycle for 3 cycles. When given on the same day, toripalimab is infused first, followed by sacituzumab tirumotecan after an interval of at least 30 minutes.
Hebei Medical University Fourth Hospital
Shijiazhuang, Hebei, China
Pathologic complete response (pCR) rate
The proportion of participants with no residual viable tumor cells in the resected primary tumor and regional lymph nodes (ypT0N0) after neoadjuvant therapy, as assessed by central pathologic review.
Time frame: Approximately 3 months after the first dose (after completion of neoadjuvant therapy and radical surgery)
Major pathologic response (MPR) rate
The proportion of participants with 10 percent or fewer viable tumor cells remaining in the resected primary tumor and regional lymph nodes after neoadjuvant therapy.
Time frame: Approximately 3 months after the first dose(after completion of neoadjuvant therapy and radical surgery)
Objective response rate (ORR) per RECIST v1.1
The proportion of participants with a confirmed complete response (CR) or partial response (PR) as assessed by the investigator according to RECIST v1.1.
Time frame: Approximately 3 months after the first dose
Event-free survival (EFS)
Time from the first dose to any of the following events: any disease progression that precludes surgery, postoperative disease progression or recurrence, or death from any cause, whichever occurs first, as assessed by the investigator according to RECIST v1.1.
Time frame: From the first dose until the event, assessed up to approximately 3 years
Overall survival (OS)
Time from the first dose to death from any cause.
Time frame: From the first dose until death from any cause, assessed up to approximately 5 years
Incidence and severity of adverse events (safety and tolerability)
Incidence, severity, and relationship to study treatment of all adverse events (AEs), treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs) graded according to NCI CTCAE v5.0; the proportion of participants requiring dose reduction or discontinuation due to AEs; and changes in vital signs, physical examination findings, and laboratory results.
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Time frame: From the first dose until 30 days after the last dose