Programmed Death Ligand (PD-L1) Combined With Chemotherapy for Patients With BTC (KN035-BTC)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Biliary Tract Neoplasms
• Intervention / Treatment: Drug: KN035 plus Gemcitabine & oxaliplatin; Drug: Gemcitabine & oxaliplatin

• Study Type: Interventional
• Enrollment (Estimated): 480
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Lan Qin; Phone Number: +86(10) 64882533; Email: lan.qin@3d-medicines.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210002
      • Recruiting
      • The Chinese people's liberation army (PLA) 81hospital
      • Contact: Xiufeng Liu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KN035; 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; KN035 a programmed death ligand immune check inhibitor Per Investigator decision; Other Names: Experimental
Active Comparator: Gemcitabine & oxaliplatin; 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; The standard of care for the patients with unresectable/metastatic biliary tract cancer; Other Names: Active Comparator

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: 3D Medicines (Sichuan) Co., Ltd.
• Investigators: Principal Investigator: Shukui Qin, The Chinese people's liberation army (PLA) 81 hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2018
• Primary Completion (Estimated): January 31, 2024
• Study Completion (Estimated): July 30, 2024

Study Registration Dates

• First Submitted: March 21, 2018
• First Submitted That Met QC Criteria: March 21, 2018
• First Posted (Actual): March 27, 2018

Study Record Updates

• Last Update Posted (Actual): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Biliary Tract Diseases; Biliary Tract Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Oxaliplatin; Gemcitabine
• Other Study ID Numbers: KN035-CN-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No