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

NCT07823270 | Not Yet Recruiting Phase 2

• 1 other identifier: ESCC-IIT-JS001-N08
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Esophageal Squamous Cell Carcinoma

Keywords

esophageal squamous cell carcinoma; neoadjuvant therapy; TROP2 antibody-drug conjugate

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Major pathologic response (MPR) rate

  Approximately 3 months after the first dose(after completion of neoadjuvant therapy and radical surgery)

• Objective response rate (ORR) per RECIST v1.1

  Approximately 3 months after the first dose

• Event-free survival (EFS)

  From the first dose until the event, assessed up to approximately 3 years

• Overall survival (OS)

  From the first dose until death from any cause, assessed up to approximately 5 years

• Incidence and severity of adverse events (safety and tolerability)

  From the first dose until 30 days after the last dose

Study Arms (1)

Neoadjuvant Sacituzumab Tirumotecan + Toripalimab

EXPERIMENTAL

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; Drug: Toripalimab

Interventions

Sacituzumab tirumotecan DRUG

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.

Neoadjuvant Sacituzumab Tirumotecan + Toripalimab

Toripalimab DRUG

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.

Neoadjuvant Sacituzumab Tirumotecan + Toripalimab

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hebei Medical University Fourth Hospital: lead

Study Sites (1)

Hebei Medical University Fourth Hospital

Shijiazhuang, Hebei, 050011, China

Location

Related Publications (3)

• 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.

  PMID: 35245446 BACKGROUND

• 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.

  PMID: 34160577 BACKGROUND

• 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.

  PMID: 26254683 BACKGROUND

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

toripalimab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Study Officials

• Ziqiang Tian

  Hebei Medical University Fourth Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhenhua Li

CONTACT

+86 185 3111 5825

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2026
• First Posted: September 16, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2030
• Last Updated: September 16, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)