KN046 in Patients With Recurrent or Metastatic Esophageal Squamous Cell Carcinoma

Study Overview
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Brief Summary
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This is an open-label, phase II study of KN046 combined with chemotherapy and palliative radiotherapy in patients with recurrent or metastatic esophageal squamous cell carcinoma to evaluate the safety, efficacy and tolerance.

Official Title
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Phase II Study of KN046 in Patients With Recurrent or Metastatic Esophageal Squamous Cell Carcinoma to Evaluate Safety, Efficacy and Tolerance

Conditions
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Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: KN046
* Radiation: palliative radiotherapy
* Drug: KN046


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed inform consent form(ICF) Age ≥ 18 years and ≤ 75 years, male or female Histologically or cytologically documented recurrent or metastatic esophageal squamous cell carcinoma, with indications of radiotherapy and without prior systemic treatment At least one measurable lesion according to Response Evaluation Criteria In Solid Tumors（RECISIT） v 1.1 Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Adequate organ function Female patients and males with partners of childbearing potential should be using highly effective contraceptive measures (failure rate of less than 1% per year). Contraception should be continued for a period of 24 weeks after dosing has been completed. Ability to comply with treatment, procedures and pharmacokinetics (PK) sample collection and the required study follow-up procedures Exclusion Criteria: Known brain metastasis or another Central Nervous System (CNS) metastasis that is either symptomatic or untreated. Patients who are participating or have participated in a study of an investigational drug within 4 weeks prior to the first dose of trial treatment. Patients who have received immune checkpoint proteins/antibody/medicine for treatment. Patients who have interstitial lung disease, or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management. Subjects with active autoimmune diseases or history of autoimmune diseases should be excluded Active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection. Known HIV infection or known history of acquired immune deficient syndrome (AIDS) Any unresolved the Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 2 toxicities from prior anti-cancer therapy except for vitiligo, alopecia Patients who have serious hypersensitive reaction to monoclonal antibodies and have history of uncontrolled allergic asthma

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Concurrent chemoradiotherapy and KN046<br>Participants in the Arm I will receive chemoradiotherapy and concurrent KN046. Radiotherapy will be completed within the four-cycle of chemotherapy. | Drug: KN046<br>* Cisplatin+paclitaxel will be administered once every three weeks for four cycles. During the period of radiotherapy, KN046 will be administered once every two weeks until progressive disease, unacceptable toxicity or up to 2 years.<br>* Other names: Cisplatin+paclitaxel;Radiation: palliative radiotherapy<br>* 3D conformal radiation therapy will be administered for esophageal lesion or nearby lymph node. Stereotactic body radiation will be administered for metastatic lesion.<br>|
| Experimental: chemoradiotherapy and sequential KN046<br>Participants in the Arm II will receive chemoradiotherapy and sequential KN046. Radiotherapy will be completed within the four-cycle of chemotherapy. | Radiation: palliative radiotherapy<br>* 3D conformal radiation therapy will be administered for esophageal lesion or nearby lymph node. Stereotactic body radiation will be administered for metastatic lesion.<br>Drug: KN046<br>* Cisplatin+paclitaxel will be administered once every three weeks for four cycles. After completion of radiotherapy, KN046 will be administered once every two weeks until progressive disease, unacceptable toxicity or up to 2 years.<br>* Other names: Cisplatin+paclitaxel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| dose-limiting toxicity KN046 |  | 28 days after first dose | 
| 6-month progression free survival rate assessed by investigator based on RECIST 1.1 |  | 6 months after first dose | 
| Objective response rate assessed by investigator based on RECIST 1.1 |  | 2 years |