KC1036 plus a PD-1 antibody and platinum chemotherapy for first-line advanced esophageal cancer

A Phase II Clinical Study to Evaluate the Efficacy and Safety of KC1036 Combined With PD-1 Antibody and Platinum-based Chemotherapy as First-line Treatment for Advanced Recurrent or Metastatic Esophageal Squamous Cell Carcinoma

This trial will test whether adding the oral drug KC1036 to a PD-1 antibody (toripalimab) with paclitaxel and cisplatin helps people with unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma as first-line treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Beijing Konruns Pharmaceutical Co., Ltd. (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, toripalimab
• Locations: 1 site (Beijing)
• Trial ID: NCT07481058 on ClinicalTrials.gov

What this trial studies

This is a multicenter Phase II study combining oral KC1036 with the PD-1 antibody toripalimab and standard platinum-based chemotherapy (paclitaxel and cisplatin) for first-line treatment of advanced esophageal squamous cell carcinoma. The trial includes a Phase IIa dose-escalation and expansion component testing KC1036 at 20, 30, or 40 mg once daily to characterize safety, followed by a randomized Phase IIb evaluation with 2–3 cohorts (up to ~50 subjects per arm) to help identify a recommended dose for further study. Treatments are given every three weeks with KC1036 taken daily and continued until confirmed disease progression by RECIST v1.1, unacceptable toxicity, death, or start of another anti-tumor therapy. Safety, tumor response, and tolerability are the main outcomes guiding dose selection and further development.

Who should consider this trial

Good fit: Adults aged 18–75 with histologically confirmed esophageal or esophagogastric junction squamous cell carcinoma that is unresectable locally advanced, recurrent, or metastatic, who have measurable disease, ECOG performance status 0–1, adequate organ function, and no prior systemic therapy for the current metastatic/recurrent disease are ideal candidates.

Not a fit: Patients with symptomatic or untreated progressing CNS metastases, other recent malignancies, known hypersensitivity to study drugs, poor organ function, ECOG >1, prior systemic therapy for the current disease, or those who cannot take part in required visits are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the combination could improve tumor response rates and extend progression-free and possibly overall survival beyond chemotherapy plus PD-1 antibody alone.

How similar studies have performed: Combining PD-1 antibodies with platinum‑based chemotherapy has previously improved outcomes in first‑line ESCC, but adding a novel oral agent like KC1036 is experimental and not yet proven.

Eligibility criteria

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.

Where this trial is running

Beijing

• Cancer Hospital, Chinese Academy of Medical Sciences — Beijing, China (Recruiting)

Study contacts

• Study coordinator: Jing Huang, Ph.D

Conditions Esophageal Squamous Cell Carcinoma