Esophageal Squamous Cell Carcinoma
Conditions
Brief summary
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.
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.
Interventions
DRUGSKB500
SKB500 will be administered as an intravenous infusion(IV), every 3 weeks on Day 1 of each 21-day cycle.
DRUGTislelizumab
Tislelizumab will be administered as an intravenous infusion(IV) every 3 weeks on Day 1 of each 21-day cycle .
DRUGCisplatin
Cisplatin will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.
DRUG5 - FU
5-FU will be administered as an intravenous infusion(IV) every 3 weeks on Day 1-5 of each 21-day cycle.
Sponsors
Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | up to 24 months | 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. |
| Incidence and severity of adverse events (AEs) and serious adverse event(SAEs) | up to 24 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | up to 24 months | 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. |
| Duration of response (DOR) | up to 24 months | 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. |
| Disease control rate (DCR) | up to 24 months | Disease control rate (DCR) was defined as the sum of complete response (CR) rate, partial response (PR) rate, and stable disease (SD) rate. |
| Overall Survival (OS) | up to 24 months | The time from first dose to death from any cause. |
| Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of SKB500-ADC, SKB500-TAB and free payload | up to 24 months | 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). |
| Pharmacokinetic Parameter Minimum Plasma Concentration (Cmin) of SKB500-ADC, SKB500-TAB and free payload | up to 24 months | 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) . |
| Anti-drug Antibodies (ADA) for SKB500 | up to 24 months | Cycle 1, 2, 4, 8, every subsequent 8 cycles starting from Cycle 8 Day 1 : pre-dose (each cycle is 21 days). |
Countries
China
Contacts
CONTACTQing Yan
Outcome results
None listed