SKB500 Combinations in Patients With Esophageal Squamous Cell Carcinoma

A Phase II, Multicenter, Open-Label Study to Evaluate the Safety and Efficacy of SKB500 Combinations in Patients With Esophageal Squamous Cell Carcinoma

The purpose of this study is to evaluate the safety, tolerability and preliminary antitumor activity of SKB500 combinations in patients with Esophageal Squamous Cell Carcinoma. The study is divided into three parts: the safety run-in phase, randomized enrollment phase and cohort expansion phase.

Study Overview

• Status: Not yet recruiting
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: SKB500; Drug: Tislelizumab; Drug: 5 - FU; Drug: Cisplatin

Detailed Description

This is a Phase II, multicenter, open-label study to evaluate the safety, tolerability and preliminary antitumor activity of SKB500 combinations in patients with Esophageal Squamous Cell Carcinoma. The study is divided into three parts: the safety run-in phase, randomized enrollment phase and cohort expansion phase.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Qing Yan; Phone Number: 028-67255480; Email: qingyan@kelun.com

Study Locations

• China
  • Changchun, China
    • Jilin Cancer Hospital
  • Chengdu, China
    • West China Hospital, Sichuan University
  • Chengdu, China
    • Chengdu Fifth People's Hospital
  • Chengdu, China
    • Sichuan Cancer Hospital & Institute
  • Chongqing, China
    • Chongqing University Three Gorges Hospital
  • Fuzhou, China
    • Fujian Cancer Hospital
  • Ha’erbin, China
    • Harbin Medical University Cancer Hospital
  • Jinan, China
    • Cancer Hospital of Shandong First Medical University
    • Contact: Yu Jinming; Phone Number: 0531-67626063; Email: sdyujinming@126.com
  • Kunming, China
    • Yunnan Cancer Hospital
  • Luoyang, China
    • The First Affiliated Hospital of Henan University of science and Technology
  • Nanchang, China
    • The Second Affiliated hospital of Nanchang University
  • Nanjing, China
    • Jiangsu Province Hospital
  • Nanjing, China
    • Jiangsu Cancer Hospital
  • Nanning, China
    • Guangxi Medical University Cancer Hospital
  • Shenyang, China
    • Cancer Hospital of Dalian University of Technology
  • Shijiazhuang, China
    • The Fourth Hospital of Hebei Medical University
  • Shiyan, China
    • Shiyan Renmin Hospital
  • Taiyuan, China
    • Shanxi Cancer Hospital
  • Tianjin, China
    • Tianjin Medical University Cancer Institute & Hospital
  • Xi'an, China
    • The First Affiliated Hospital of Xi'an Jiaotong University
  • Yichang, China
    • Yichang Central People's Hospital
  • Zhengzhou, China
    • Henan Cancer Hospital
  • Zhengzhou, China
    • The First Affiliated Hospital of Zhengzhou University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥18 years and ≤75 years

2. Histologically or cytologically confirmed unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC), who are ineligible for curative-intent therapies:

   • Safety run-in phase (Cohort 1, 2 and 3): received no more than 1 prior line of systemic therapy for locally advanced or metastatic ESCC.
   • Safety run-in phase (Cohort 4), randomized enrollment phase and cohort expansion phase: no prior systemic therapy for locally advanced or metastatic ESCC.
3. Participants are required to provide tumor tissue samples for biomarker analysis.
4. Has at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Life expectancy ≥ 12 weeks.

Exclusion Criteria:

1. Histology or cytology confirms the presence of concurrent adenocarcinoma components.
2. Leptomeningeal, brainstem, spinal, spinal cord compression, or active CNS metastases.
3. Risk of esophagotracheal/esophagopleural fistula, or symptomatic invasion/compression of vital organs/major blood vessels.
4. Active autoimmune disease requiring systemic therapy within past 2 years.
5. Weight loss ≥10% within 4 weeks prior to the first dose, or Nutritional Risk Index (NRI) < 83.5.
6. Severe infection within 4 weeks or active infection requiring systemic treatment within 2 weeks pre-dose.
7. Uncontrolled comorbidities (e.g., decompensated liver cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders, Grade ≥2 peripheral neuropathy).
8. Cardiovascular/cerebrovascular events within 6 months pre-dose (e.g., Myocardial Infarction, unstable angina, acute/persistent ischemia, Grade 3/4 Heart Failure, symptomatic/uncontrolled arrhythmia, Cerebrovascular Accident, Transient Ischemic Attack).
9. Uncontrolled hypertension, diabetes, or recurrent pleural/pericardial/abdominal effusion requiring drainage.
10. History of interstitial lung disease (ILD) or noninfectious pneumonitis that require steroid treatment, or currently has ILD/noninfectious pneumonitis.
11. Unresolved to grade ≤ 1 of prior anti-cancer treatment toxicities criteria per CTCAE v6.0.
12. Previously received B7-H3-targeted agents, including antibody, antibodydrug conjugate (ADC), and other agents.
13. Previously received treatment with an ADC that consists of a topoisomerase l inhibitor.
14. Pregnant or lactating women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1. SKB500+Tislelizumab; Participants will receive Tislelizumab followed by SKB500	Drug: SKB500; SKB500 will be administered as an intravenous infusion(IV), every 3 weeks on Day 1 of each 21-day cycle.; Drug: Tislelizumab; Tislelizumab will be administered as an intravenous infusion(IV) every 3 weeks on Day 1 of each 21-day cycle .
Experimental: Cohort 2. SKB500+Tislelizumab+5-FU; Participants will receive Tislelizumab followed by SKB500, 5-FU	Drug: SKB500; SKB500 will be administered as an intravenous infusion(IV), every 3 weeks on Day 1 of each 21-day cycle.; Drug: Tislelizumab; Tislelizumab will be administered as an intravenous infusion(IV) every 3 weeks on Day 1 of each 21-day cycle .; Drug: 5 - FU; 5-FU will be administered as an intravenous infusion(IV) every 3 weeks on Day 1-5 of each 21-day cycle.
Experimental: Cohort 3. SKB500+Tislelizumab+ Cisplatin; Participants will receive Tislelizumab followed by SKB500, Cisplatin	Drug: SKB500; SKB500 will be administered as an intravenous infusion(IV), every 3 weeks on Day 1 of each 21-day cycle.; Drug: Tislelizumab; Tislelizumab will be administered as an intravenous infusion(IV) every 3 weeks on Day 1 of each 21-day cycle .; Drug: Cisplatin; Cisplatin will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.
Experimental: Cohort 4. SKB500+Tislelizumab+ Cisplatin+5-FU; Participants will receive Tislelizumab followed by SKB500, Cisplatin, 5-FU	Drug: SKB500; SKB500 will be administered as an intravenous infusion(IV), every 3 weeks on Day 1 of each 21-day cycle.; Drug: Tislelizumab; Tislelizumab will be administered as an intravenous infusion(IV) every 3 weeks on Day 1 of each 21-day cycle .; Drug: 5 - FU; 5-FU will be administered as an intravenous infusion(IV) every 3 weeks on Day 1-5 of each 21-day cycle.; Drug: Cisplatin; Cisplatin will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR), assessed by investigator based on RECIST version 1.1.	up to 24 months
Incidence and severity of adverse events (AEs) and serious adverse event(SAEs)	Incidence and severity of adverse events (AEs) and serious adverse event(SAEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v6.0, as well as clinically significant abnormal laboratory findings.	up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Progression-free survival (PFS) was defined as the time from baseline to the earliest date of the first objective documentation of progressive disease (PD) or death due to any cause.	up to 24 months
Overall Survival (OS)	The time from first dose to death from any cause.	up to 24 months
Duration of response (DOR)	Duration of Response (DOR) was defined as the time from the date of the first documentation of objective response (complete response[CR] or partial response [PR]) to the date of the first objective documentation of progressive disease (PD) or death due to any cause. DOR was measured for responding participants (PR or CR) only.	up to 24 months
Disease control rate (DCR)	Disease control rate (DCR) was defined as the sum of complete response (CR) rate, partial response (PR) rate, and stable disease (SD) rate.	up to 24 months
Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of SKB500-ADC, SKB500-TAB and free payload	Cycle 1, 2, 4, 6, 8: pre-dose, post-dose; 12,16, every 8 cycles starting from Cycle 16 Day 1: pre-dose(each cycle is 21 days).	up to 24 months
Pharmacokinetic Parameter Minimum Plasma Concentration (Cmin) of SKB500-ADC, SKB500-TAB and free payload	Cycle 1, 2, 4, 6, 8: pre-dose, post-dose; 12,16, every 8 cycles starting from Cycle 16 Day 1: pre-dose(each cycle is 21 days) .	up to 24 months
Anti-drug Antibodies (ADA) for SKB500	Cycle 1, 2, 4, 8, every subsequent 8 cycles starting from Cycle 8 Day 1 : pre-dose (each cycle is 21 days).	up to 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers	Correlation between the expression level of PD-L1, B7-H3, SLFN11 in tumor tissues and the efficacy.	During the screening period, tumor tissue samples should be provided for PD-L1, B7-H3, SLFN11 testing

Collaborators and Investigators

• Sponsor: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): July 30, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: July 8, 2026
• First Submitted That Met QC Criteria: July 8, 2026
• First Posted (Actual): July 14, 2026

Study Record Updates

• Last Update Posted (Actual): July 14, 2026
• Last Update Submitted That Met QC Criteria: July 8, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• 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; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Pyrimidines; Uracil; Pyrimidinones; Platinum Compounds; Fluorouracil; Cisplatin; tislelizumab
• Other Study ID Numbers: SKB500-Ⅱ-04

Drug and device information, study documents

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