Esophageal Squamous Cell Carcinoma (ESCC)
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of KC1036 in combination with PD-1 antibody and platinum-based chemotherapy as a first-line treatment for patients with unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC).
Detailed description
This multicenter Phase II study evaluates KC1036 in combination with PD-1 antibody and platinum-based chemotherapy as first-line treatment for advanced esophageal squamous cell carcinoma. The trial comprises a Phase IIa dose-escalation and expansion phase to assess the safety of KC1036 at 20, 30, or 40 mg QD, followed by a Phase IIb randomized evaluation of 2-3 cohorts (up to 50 subjects per arm) to identify the recommended Phase III dose. Subjects receive daily oral KC1036 plus toripalimab, paclitaxel, and cisplatin every 3 weeks until confirmed disease progression assessed by the RECIST V1.1 standard, death, intolerable toxicity, initiation of a new anti-tumor therapy, other reasons leading to treatment discontinuation as specified by protocol.
Interventions
DRUGKC1036
Dosage: 20 mg, 30 mg, or 40 mg; Route: Oral; Frequency: Once daily (QD) under fasting conditions (at least 2 hours before and 1 hour after dosing), 21 days as a cycle.
DRUGToripalimab
Dosage: 240 mg; Route: Intravenous (IV) infusion; Frequency: Every 3 weeks (Q3W) on Day 1 of each 21-day cycle, for up to 2 years.
DRUGPaclitaxel
Dosage: 175 mg/m2; Route: IV infusion; Frequency: Day 1 of each 21-day cycle, for a maximum of 6 cycles.
DRUGCisplatin
Dosage: 60-75 mg/m2; Route: IV infusion; Frequency: Day 1 of each 21-day cycle, for a maximum of 6 cycles.
Sponsors
Beijing Konruns Pharmaceutical Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Males or females aged 18 to 75 years; * Histologically or cytologically confirmed esophageal or esophageal-gastric junction squamous cell carcinoma; * Patients who have not received prior systemic anti-tumor therapy for the current recurrent or metastatic disease; * At least one measurable tumor lesion according to RECIST 1.1; * Eastern Cooperative Oncology Group performance status score of 0 or 1; * Life expectancy \> 12 weeks; * BMI≥16.0 kg/m2; * Adequate bone marrow, renal, and hepatic function; * Female patients of childbearing potential with a negative blood pregnancy test completed within 7 days before the first dose; * Patients should participate in the study voluntarily and sign informed consent.
Exclusion criteria
* Symptomatic, untreated, or actively progressing central nervous system (CNS) metastasis; * Other malignancies within the past 5 years; * Known hypersensitivity to any monoclonal antibodies or chemotherapy components; * Gastrointestinal abnormalities; * High risk of bleeding or fistula due to tumor invasion of adjacent organs, or existing esophageal/tracheal fistula; * Cardiovascular and cerebrovascular diseases; * Prior therapy with anti-angiogenic drugs or immunotherapy; Systemic therapy, investigational drugs, or live vaccines within 4 weeks prior to the first dose; Palliative radiotherapy within 2 weeks or major surgery within 28 days prior to enrollment; * Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage; * Presence of unresolved toxicities from prior anti-tumor therapy, defined as having not resolved to NCI CTCAE 5.0 Grade 0 or 1; * Active autoimmune disease or a history of autoimmune disease requiring systemic treatment; * Active infections, including severe infection (CTCAE \> Grade 2) within 4 weeks, active tuberculosis, or positive status for HIV, HBV, or HCV; * Pregnant or lactating women; * Female subjects of child-bearing potential and male subjects of reproductive capacity who do not agree to use contraceptive measures during the study and for 6 months after the end of the study; * Other conditions assessed by the investigator that would increase safety risks or interfere with the study results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Baseline to study completion (approximately 24 months) | ORR is defined as the proportions of patients with a complete response (CR) or partial response (PR) according to RECIST 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | Baseline to study completion (approximately 24 months) | PFS is defined as the time from the first study drug administration to the date of the first documented progressive disease (PD) according to RECIST 1.1 or death. |
| Disease Control Rate (DCR) | Baseline to study completion (approximately 24 months) | DCR is defined as the percentage of participants with a best overall complete response (CR), partial response (PR), or stable disease (SD) according to RECIST 1.1. |
| Duration of Response (DOR) | Baseline to study completion (approximately 24 months). | DOR is defined as the time from first documented objective response (complete response (CR)or partial response (PR)) to the date of first documented disease progression (PD) or death. |
| TTR | Baseline to study completion (approximately 24 months) | TTR is defined as the time from the start of the first study drug administration to the date of the first documented response of complete response (CR) or partial response (PR) according to RECIST 1.1. |
| Adverse events (AEs) | Baseline to 30 days after the last dose of study treatment | Assessed by treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) during the treatment assessed by NCI CTCAE 5.0. |
Countries
China
Contacts
CONTACTJing Huang, Ph.D
Outcome results
None listed