Programmed Death Ligand (PD-L1) Combined With Chemotherapy for Patients With BTC

Study Overview
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Brief Summary
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This is a randomized, open-label, parallel-group multi-center study of Phase 3 study to assess the efficacy and safety of KN035 compared to standard of care (SOC) Gemcitabine-based chemotherapies in the treatment of participants with previously untreated locally advanced or metastatic biliary tract cancer. The primary hypothesis of this study is that participants will have a longer overall Survival (OS) when treated with combined therapy than SOC.

Official Title
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Gemcitabine and Oxaliplatin With or Without KN035 for Biliary Tract Cancer: a Randomised, Open-label, Parallel-group, Multicenter Phase III Study

Conditions
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Biliary Tract Neoplasms

Intervention / Treatment
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* Drug: KN035 plus Gemcitabine & oxaliplatin
* Drug: Gemcitabine & oxaliplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eighteen years and older; Histological or cytological diagnosis of unresectable or metastatic gallbladder cancer or cholangiocarcinoma; Previously untreated with systemic therapy; Subjects who developed recurrent disease >6 months after a sort of adjuvant, neoadjuvant chemotherapy could also be eligible. Liver function Child-Pugh A or B; Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status; Life expectancy of at least 12 weeks; At least one measurable lesion per RECIST 1.1; Adequate organ function Exclusion Criteria: Specific anti-tumor treatment prior to 4 weeks; more than 50% liver metastasis ; Patient with other serious diseases or clinical conditions, including but not limited to uncontrolled active infection etc; History of severe hypersensitivity reaction to any monoclonal antibody or chemistry; Women who are pregnant or in the period of lactation; Patients with an active, known or suspected autoimmune disease. Patients are permitted to enrol if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement;

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KN035<br>KN035 plus Gemcitabine & oxaliplatin KN035 2.5 mg/Kg, administered as subcutaneous injection, weekly of each 21-day cycle. Gemcitabine 1000 mg/m^2, IV infusion on Day 1 and Day 8, and oxaliplatin 85 mg/m^2, IV infusion on Day 1 of each 21-day cycle for no more than 6 cycles. | Drug: KN035 plus Gemcitabine & oxaliplatin<br>* KN035 a programmed death ligand immune check inhibitor Per Investigator decision<br>* Other names: Experimental;|
| Active Comparator: Gemcitabine & oxaliplatin<br>Gemcitabine 1000 mg/m^2, IV infusion on Day 1 and Day 8, and oxaliplatin 85 mg/m^2, IV infusion on Day 1 of each 21-day cycle for no more than 6 cycles. | Drug: Gemcitabine & oxaliplatin<br>* The standard of care for the patients with unresectable/metastatic biliary tract cancer<br>* Other names: Active Comparator;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | was defined as the time from randomization to death due to any cause. | Observed by 12 weeks after progressive disease or end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | was defined as the time from randomization to documented disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or death due to any cause, whichever occurred first and was based on blinded independent Review Committee (BIRC) review. | Observed by 6 weeks | 
| Objective response rate (ORR) | was defined as the percentage of participants in the analysis population who experienced a Complete Response or a Partial Response and was assessed using RECIST 1.1 based on BIRC evaluation. | Observed by 6 weeks | 
| Disease control rate (DCR) | was defined as the percentage of participants in the analysis population who experienced a Complete Response or a Partial Response or stable disease and was assessed using RECIST 1.1 based on BIRC evaluation | Observed by 6 weeks | 
| Duration of Response (DOR) | was defined as the time from the first met for complete response/partial response (whichever was first recorded) until the first date that recurrent or progressive disease was objectively documented (taking as reference for progressive disease the smallest measurements recorded on study) | Observed by 6 weeks | 
| Time to progression (TTP) | was defined as the time from randomization to the first date that progressive disease was objectively documented | Observed by 6 weeks |