Overview
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).
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.
Eligibility
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.
