Clinical trial NCT05242822: A Study to Evaluate KIN-3248 in Participants With Advanced Tumors Harboring FGFR2 and//or FGFR3 Gene Alterations
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumor, Adult
Intrahepatic Cholangiocarcinoma
Urothelial Carcinoma
Keywords: FGFR inhibitor
targeted therapy
FGFR2 alteration
FGFR3 alteration
secondary resistance
FGFR alteration
Lead sponsor: Kinnate Biopharma
Sponsor class: INDUSTRY
First posted: 2022-02-16
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Part A (dose escalation) - incidence of dose limiting toxicities (DLTs)
timeFrame: Initiation of study drug through 28 days
measure: Part A (dose escalation) - incidence of adverse events (AEs)
timeFrame: Initiation of study drug through 28 days after last dose (up to approximately 18 months)
measure: 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
timeFrame: Initiation of study drug until disease progression (up to approximately 36 months)
measure: Part B (dose expansion) - disease control rate (DCR): the proportion of participants who achieve stable disease, PR, or CR
timeFrame: Initiation of study drug until disease progression (up to approximately 36 months)
measure: Part B (dose expansion) - duration of response (DOR): the length of time between initial tumor response to documented tumor progression
timeFrame: Initiation of study drug until disease progression (up to approximately 36 months)
measure: Part B (dose expansion) - progression-free survival (PFS): the length of time until documented tumor progression
timeFrame: Initiation of study drug until disease progression (up to approximately 36 months)
Secondary outcomes:
measure: Part A (dose escalation) - PK - maximum plasma concentration (Cmax) of KIN-3248
timeFrame: Initiation of study drug through Cycle 5 (up to approximately 4 months)
measure: Part A (dose escalation) - PK - time to reach maximum plasma concentration (Tmax) of KIN-3248
timeFrame: Initiation of study drug through Cycle 5 (up to approximately 4 months)
measure: Part A (dose escalation) - PK - area under the plasma concentration-time curve (AUC) of KIN-3248
timeFrame: Initiation of study drug through Cycle 5 (up to approximately 4 months)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Orlando
country: United States
facility: Sarah Cannon Research Institute - Lake Nona
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: New York
country: United States
facility: NYU Langone Cancer Center
state: New York
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Haidian District
city: Copenhagen
country: Denmark
facility: Rigshospitalet (Copenhagen University Hospital) - Finsencentret - Onkologisk Klinik
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital (SNUH)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Madrid
country: Spain
facility: START (Fundacion Jimenez Diaz)
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Hospital
city: Taipei
country: Taiwan
facility: Veterans General Hospital - Taipei
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
References: