Neoadjuvant Sacituzumab Tirumotecan Plus Toripalimab in Locally Advanced Esophageal Squamous Cell Carcinoma

A Prospective, Single-arm, Phase II Study of Neoadjuvant Sacituzumab Tirumotecan (SKB264/MK-2870) Combined With Toripalimab in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Sacituzumab tirumotecan; Drug: Toripalimab

Detailed Description

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
• Enrollment (Estimated): 33
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhenhua Li; Phone Number: +86 185 3111 5825

Study Locations

• China
  • Hebei
    • Shijiazhuang, Hebei, China, 050011
      • Hebei Medical University Fourth Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age >=18 years at the time of informed consent, either sex.
• Histologically or cytologically confirmed locally advanced esophageal squamous cell carcinoma.
• Judged by imaging and esophagoscopy as resectable and requiring neoadjuvant therapy, with clinical stage cT1-2N+M0 or T3-4N0-3M0 (stage II-IVA).
• No prior antitumor therapy for esophageal squamous cell carcinoma.
• At least one measurable lesion per RECIST v1.1.
• ECOG performance status of 0 or 1 within 7 days before dosing.
• Adequate organ and bone marrow function (no transfusion, recombinant human thrombopoietin, or colony-stimulating factor within 2 weeks before the first dose):
• Hematology: NEUT# >=1.5x10^9/L; PLT >=100x10^9/L; hemoglobin >=90 g/L.
• Hepatic: AST and ALT <=2.5xULN (<=5xULN for participants with baseline liver metastases); albumin >=30 g/L; total bilirubin <=1.5xULN.
• Renal: creatinine clearance >=60 mL/min (Cockcroft-Gault formula).
• Coagulation: INR, APTT, and PT <=1.5xULN.
• Normal thyroid function, defined as TSH within the normal range. If baseline TSH is outside the normal range, participants with total T3 (or FT3) and FT4 within the normal range are also eligible.
• Cardiac enzymes within the normal range (isolated laboratory abnormalities judged by the investigator as not clinically significant are allowed).
• Left ventricular ejection fraction >=55%.
• Women of childbearing potential and men with partners of childbearing potential must agree to use effective medical contraception from informed consent until 6 months after the last dose.
• Participants voluntarily join the study, sign the informed consent form, and are able to comply with the scheduled visits and procedures.

Exclusion Criteria:

• Any prior antitumor therapy for the currently diagnosed esophageal squamous cell carcinoma.
• History of other malignancies within 5 years (except cured basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and carcinoma in situ of the cervix).
• Requirement for strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) within 2 weeks before the first dose or during the study.
• Documented severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or a history of corneal disease that interferes with or delays corneal healing.
• Any of the following cardiovascular or cerebrovascular diseases or risk factors:
• Myocardial infarction, unstable angina, acute or persistent myocardial ischemia, grade 3 or 4 heart failure (NYHA classification), symptomatic or poorly controlled severe arrhythmia, cerebrovascular accident, transient ischemic attack, or other severe cardiovascular or cerebrovascular diseases within 6 months before dosing.
• History of myocarditis, primary cardiomyopathy, or specific cardiomyopathy.
• Any deep vein thrombosis (participants stabilized with low molecular weight heparin or similar therapy for >=2 weeks may be allowed), peripheral arterial thromboembolic event, pulmonary embolism, or other severe thromboembolic events within 3 months before dosing.
• Aortic aneurysm, aortic dissecting aneurysm, or other major vascular disease that may be life-threatening or requires surgery within 6 months before dosing.
• Uncontrolled systemic disease as judged by the investigator:
• Poorly controlled diabetes mellitus (two consecutive fasting glucose levels >=9 mmol/L).
• Poorly controlled hypertension (systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg).
• Symptomatic pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
• History of steroid-requiring (non-infectious) interstitial lung disease (ILD) or non-infectious pneumonitis; current ILD or non-infectious pneumonitis; or suspected ILD or non-infectious pneumonitis that cannot be excluded by imaging at screening.
• Active autoimmune disease requiring systemic treatment within the past 2 years, including disease-modifying drugs, immunosuppressants, or systemic corticosteroids (>10 mg/day prednisone or equivalent). Hormone replacement therapy such as thyroxine, insulin, or physiologic corticosteroid replacement for adrenal or pituitary insufficiency is not considered systemic treatment. Participants receiving systemic corticosteroids >10 mg/day prednisone or other immunosuppressive drugs within 2 weeks before dosing.
• Known active pulmonary tuberculosis. Participants with suspected active pulmonary tuberculosis must undergo clinical evaluation to exclude it.
• Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Active hepatitis B (HBsAg positive with HBV-DNA >=500 IU/mL or above the lower limit of detection, whichever is higher) or hepatitis C (HCV antibody positive with HCV-RNA above the lower limit of detection). Participants who are HBsAg positive are required to receive anti-hepatitis B viral therapy during the study.
• Positive human immunodeficiency virus (HIV) test or history of acquired immunodeficiency syndrome (AIDS); known active syphilis infection.
• Known hypersensitivity to the study drugs or any of their components, or a history of severe hypersensitivity reactions to other biologics.
• Severe infection within 4 weeks before dosing, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia; active infection requiring systemic anti-infective therapy within 2 weeks before dosing.
• Receipt of non-specific immunomodulatory therapy (including but not limited to interferon, IL-2) or Chinese patent medicines approved for antitumor indications within 2 weeks before dosing.
• Receipt of a live vaccine within 30 days before dosing, or planned receipt of a live vaccine during the study.
• Rapid deterioration during screening before dosing, such as a marked change in performance status.
• Pregnant or breastfeeding women.
• Local or systemic diseases caused by non-malignant conditions, or diseases or symptoms secondary to the tumor, that may lead to high medical risk and/or uncertainty in survival evaluation, such as leukemoid reaction or cachexia.
• Any condition that, in the investigator's judgment, interferes with the evaluation of the study drug, participant safety, or interpretation of study results, or any other condition that makes the participant unsuitable for this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Neoadjuvant Sacituzumab Tirumotecan + Toripalimab; Participants receive sacituzumab tirumotecan 4 mg/kg intravenously once every 2 weeks plus toripalimab 3 mg/kg intravenously once every 2 weeks for 3 cycles, followed by radical surgery.

Drug: Sacituzumab tirumotecan; 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.; Drug: Toripalimab; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Approximately 3 months after the first dose (after completion of neoadjuvant therapy and radical surgery)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	From the first dose until 30 days after the last dose

Collaborators and Investigators

• Sponsor: Hebei Medical University Fourth Hospital
• Investigators: Principal Investigator: Ziqiang Tian, Hebei Medical University Fourth Hospital

Publications and helpful links

General Publications

• Shapiro J, van Lanschot JJB, Hulshof MCCM, van Hagen P, van Berge Henegouwen MI, Wijnhoven BPL, van Laarhoven HWM, Nieuwenhuijzen GAP, Hospers GAP, Bonenkamp JJ, Cuesta MA, Blaisse RJB, Busch ORC, Ten Kate FJW, Creemers GM, Punt CJA, Plukker JTM, Verheul HMW, Bilgen EJS, van Dekken H, van der Sangen MJC, Rozema T, Biermann K, Beukema JC, Piet AHM, van Rij CM, Reinders JG, Tilanus HW, Steyerberg EW, van der Gaast A; CROSS study group. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1090-1098. doi: 10.1016/S1470-2045(15)00040-6. Epub 2015 Aug 5.
• Wang ZX, Cui C, Yao J, Zhang Y, Li M, Feng J, Yang S, Fan Y, Shi J, Zhang X, Shen L, Shu Y, Wang C, Dai T, Mao T, Chen L, Guo Z, Liu B, Pan H, Cang S, Jiang Y, Wang J, Ye M, Chen Z, Jiang D, Lin Q, Ren W, Wang J, Wu L, Xu Y, Miao Z, Sun M, Xie C, Liu Y, Wang Q, Zhao L, Li Q, Huang C, Jiang K, Yang K, Li D, Liu Y, Zhu Z, Chen R, Jia L, Li W, Liao W, Liu HX, Ma D, Ma J, Qin Y, Shi Z, Wei Q, Xiao K, Zhang Y, Zhang Y, Chen X, Dai G, He J, Li J, Li G, Liu Y, Liu Z, Yuan X, Zhang J, Fu Z, He Y, Ju F, Liu Z, Tang P, Wang T, Wang W, Zhang J, Luo X, Tang X, May R, Feng H, Yao S, Keegan P, Xu RH, Wang F. Toripalimab plus chemotherapy in treatment-naive, advanced esophageal squamous cell carcinoma (JUPITER-06): A multi-center phase 3 trial. Cancer Cell. 2022 Mar 14;40(3):277-288.e3. doi: 10.1016/j.ccell.2022.02.007. Epub 2022 Mar 3.
• Yang H, Liu H, Chen Y, Zhu C, Fang W, Yu Z, Mao W, Xiang J, Han Y, Chen Z, Yang H, Wang J, Pang Q, Zheng X, Yang H, Li T, Zhang X, Li Q, Wang G, Chen B, Mao T, Kong M, Guo X, Lin T, Liu M, Fu J. Long-term Efficacy of Neoadjuvant Chemoradiotherapy Plus Surgery for the Treatment of Locally Advanced Esophageal Squamous Cell Carcinoma: The NEOCRTEC5010 Randomized Clinical Trial. JAMA Surg. 2021 Aug 1;156(8):721-729. doi: 10.1001/jamasurg.2021.2373.

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: September 11, 2026
• First Submitted That Met QC Criteria: September 11, 2026
• First Posted (Actual): September 16, 2026

Study Record Updates

• Last Update Posted (Actual): September 16, 2026
• Last Update Submitted That Met QC Criteria: September 11, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: neoadjuvant therapy; esophageal squamous cell carcinoma; TROP2 antibody-drug conjugate
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Carcinoma; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; toripalimab
• Other Study ID Numbers: ESCC-IIT-JS001-N08

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No