This study is a multicenter, open-label, single-arm, phase Ib/II clinical study comprising two phases: dose confirmation phase and dose expansion phase. The objective of the dose confirmation phase is to determine the recommended Phase II dose (RP2D) of IN10018+ standard chemotherapy (albumin-bound paclitaxel + gemcitabine) and IN10018 + KN046 + standard chemotherapy in subjects with advanced pancreatic cancer. The dose expansion phase will further explore the antitumor activities and safety of combination therapy in subjects with advanced pancreatic cancer.
This is a multicenter, open-label, single-arm, phase Ib/II clinical study to evaluate the safety, tolerability, and antitumor activities of IN10018 + standard chemotherapy (albumin paclitaxel + gemcitabine) and IN10018 + KN046 + standard chemotherapy in subjects with advanced pancreatic cancer. This study includes two cohorts, Cohort 1: IN10018 + standard chemotherapy; Cohort 2: IN10018 + standard chemotherapy + KN046. Each cohort consists of 2 phases: a dose confirmation phase and a dose expansion phase. The dose confirmation phase aims to determine recommended Phase II dose (RP2D) of IN10018+ standard chemotherapy and IN10018 + KN046 + standard chemotherapy in subjects with advanced pancreatic cancer. The dose expansion phase will further explore the antitumor activities and safety of combination therapy in subjects with advanced pancreatic cancer. According to the Package Insert of standard chemotherapy (albumin paclitaxel and gemcitabine), the Investigator's Brochure (IB) and drug characteristics of KN046, it is expected that IN10018 has little possibility of interaction with standard chemotherapy and KN046, and the safety characteristics are clearly non-overlapping. The therapeutic dose of KN046, albumin-bound paclitaxel and gemcitabine are fixed in this study. In the dose confirmation phase, IN10018 dose will be modified according to the causality between dose-limiting toxicities (DLTs) and IN10018.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
70
IN10018 orally once daily at approximately the same time each day, to ensure a dosing interval of approximately 24 hours.
Albumin-bound paclitaxel will be administered as per the schedule specified in the respective arm.
Gemcitabine will be administered as per the schedule specified in the respective arm.
KN046 5 mg/kg on Day 1 of each 21-Day Cycle.
Renji Hospital of Shanghai Jiaotong University School of Medicine
Shanghai, Shanghai Municipality, China
RECRUITINGIncidence of Treatment-Related Adverse Events (AEs)
Incidence and severity of AEs, with severity determined according to the NationalCancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
Time frame: 1 year
To evaluate the objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) in subjects with advanced pancreatic cancer.
Proportion of subjects who have the best objective response of either complete response (CR) or partial response (PR), as assessed by the investigator.
Time frame: 2 years
Disease Control Rate (DCR) per RECIST 1.1, as evaluated by investigators
Proportion of subjects who have CR, PR, or stable disease (SD).
Time frame: 1 year
duration of response (DoR) per RECIST 1.1, as evaluated by investigators
Available for subjects who demonstrate CR or PR, DoR is defined as the time from the first evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first, as assessed by the investigator.
Time frame: 1 years
Progression free survival (PFS) per RECIST 1.1, as evaluated by investigators
Defined as the time from the first day of study treatment to the first disease progression or death due to any cause, whichever occurs first.
Time frame: 1 years
Overall survival (OS)
Defined as the time from the first day of study treatment to death due to any cause.
Time frame: 2 years
Incidence of Treatment-Related AEs
Incidence and severity of AEs, with severity determined according to the NCI CTCAE v5.0
Time frame: 2 years
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