This is a Phase1, open-label, dose escalation and expansion study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of KNT-0916 in patients with unresectable or metastatic solid tumors harboring FGFR2 alterations who have failed prior systemic therapy. This study is divided into 2 parts, dose escalation part(part A), dose expansion part(partB).
This study is divided into 2 parts, part a isNdesigned to explore the maximum toxicity dose (MTD) of KNT-0916 with an accelerated titration plus traditional "3+3" design; part b is designed to explore the elementary anti-neoplastic activity of KNT-0916 with recommended dose in patients with confirmed FGFR2 alterations through central laboratory testing.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
151
• KNT-0916 is an oral inhibitor of FGFR2.
Dose-limiting Toxicity (DLT)
Time frame: 4 weeks
Maximum tolerated dose (MTD) or Maximum administered dose (MAD)
Time frame: 12 months
Incidence, relatedness, seriousness and severity of adverse events (AEs) per the National Cancer Institute Common Terminology Criteria for AE (NCI CTCAE) Version 5.0.
Time frame: 33 months
Recommended phase 2 dose (RP2D)
Time frame: 33 months
Objective response rate (ORR) assessed as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Time frame: 33 months
Duration of response (DoR) assessed as per RECIST 1.1
Time frame: 33 months
Disease control rate (DCR) assessed as per RECIST 1.1
Time frame: 33 months
Progression-free survival (PFS) assessed as per RECIST 1.1
Time frame: 33 months
Overall survival (OS) assessed as per RECIST 1.1
Time frame: 33 months
Pharmacokinetic parameters including maximum plasma drug concentration (Cmax)
Time frame: 33 months
Pharmacokinetic parameters including area under the plasma concentration versus time curve (AUC)
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Time frame: 33 months
Pharmacokinetic parameters including half-life (t1/2)
Time frame: 33 months
Pharmacokinetic parameters including time to maximum concentration (Tmax)
Time frame: 33 months
Pharmacokinetic parameters including Apparent clearance (CL/F)
Time frame: 33 months