A Study to Evaluate KIN-3248 in Participants With Advanced Tumors Harboring FGFR2 and//or FGFR3 Gene Alterations

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of KIN-3248, an oral small molecule FGFR inhibitor, in adults with advanced tumors harboring FGFR2 and/or FGFR3 gene alterations.

Detailed Description
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This is a two-part, open label, multi-center, dose escalation and dose expansion study in participants with advanced tumors harboring FGFR2 and/or FGFR3 gene alterations. Part A (dose escalation) is aimed at evaluating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of KIN-3248, and determining the maximum tolerated dose (MTD) of daily dosing of KIN-3248. Part B (dose expansion) may open once either the MTD and/or a biologically active dose of KIN-3248 is identified. Part B is aimed at evaluating the safety and efficacy of KIN-3248 at the recommended dose and schedule in participants with cancers harboring FGFR2 and/or FGFR3 gene alterations, including intrahepatic cholangiocarcinoma (ICC), urothelial cancer (UC), and other solid tumors.

Official Title
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A Phase 1/1b, Open-label, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Anti-tumor Activity of KIN-3248 in Participants With Advanced Tumors Harboring FGFR2 and/or FGFR3 Gene Alterations

Conditions
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Solid Tumor, Adult, Intrahepatic Cholangiocarcinoma, Urothelial Carcinoma

Intervention / Treatment
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* Drug: KIN-3248


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide written informed consent prior to initiation of any study-specific procedures Advanced stage solid tumor Known FGFR2 and/or FGFR3 gene alteration, as confirmed by previous genomic analysis of tumor tissue or ctDNA Measurable or evaluable disease according to RECIST v1.1 ECOG performance status 0 or 1 Adequate organ function, as measured by laboratory values (criteria listed in protocol) Able to swallow, retain, and absorb oral medications Exclusion Criteria: Known clinically-active or clinically-progressive brain metastases from non-brain tumors History and/or current evidence of abnormal calcium-phosphorous homeostasis, ectopic mineralization or calcification, or corneal or retinal disorder/keratopathy GI tract disease causing an inability to take oral medication, malabsorption syndrome, requirement for intravenous alimentation, or uncontrolled inflammatory GI disease Active, uncontrolled bacterial, fungal, or viral infection Women who are lactating or breastfeeding, or pregnant

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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A - dose escalation<br>Dose escalation of KIN-3248 in patients with solid tumors | Drug: KIN-3248<br>* KIN-3248 will be administered orally once daily in 28-day cycles<br>|
| Experimental: Part B - dose expansion<br>Dose expansion evaluating the recommended dose and schedule of KIN-3248 identified from Part A | Drug: KIN-3248<br>* KIN-3248 will be administered orally once daily in 28-day cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A (dose escalation) - incidence of dose limiting toxicities (DLTs) |  | Initiation of study drug through 28 days | 
| Part A (dose escalation) - incidence of adverse events (AEs) |  | Initiation of study drug through 28 days after last dose (up to approximately 18 months) | 
| Part B (dose expansion) - objective response rate (ORR): the proportion of participants who have achieved partial response (PR) or complete response (CR) according to RECIST v1.1 |  | Initiation of study drug until disease progression (up to approximately 36 months) | 
| Part B (dose expansion) - disease control rate (DCR): the proportion of participants who achieve stable disease, PR, or CR |  | Initiation of study drug until disease progression (up to approximately 36 months) | 
| Part B (dose expansion) - duration of response (DOR): the length of time between initial tumor response to documented tumor progression |  | Initiation of study drug until disease progression (up to approximately 36 months) | 
| Part B (dose expansion) - progression-free survival (PFS): the length of time until documented tumor progression |  | Initiation of study drug until disease progression (up to approximately 36 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A (dose escalation) - PK - maximum plasma concentration (Cmax) of KIN-3248 |  | Initiation of study drug through Cycle 5 (up to approximately 4 months) | 
| Part A (dose escalation) - PK - time to reach maximum plasma concentration (Tmax) of KIN-3248 |  | Initiation of study drug through Cycle 5 (up to approximately 4 months) | 
| Part A (dose escalation) - PK - area under the plasma concentration-time curve (AUC) of KIN-3248 |  | Initiation of study drug through Cycle 5 (up to approximately 4 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FGFR2 alteration, FGFR3 alteration, secondary resistance, FGFR alteration, FGFR inhibitor, targeted therapy