A Study to Evaluate KIN-3248 in Participants With Advanced Tumors Harboring FGFR2 and//or FGFR3 Gene Alterations
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part A - dose escalation Dose escalation of KIN-3248 in patients with solid tumors |
Drug: KIN-3248
KIN-3248 will be administered orally once daily in 28-day cycles
|
| Experimental: Part B - dose expansion Dose expansion evaluating the recommended dose and schedule of KIN-3248 identified from Part A |
Drug: KIN-3248
KIN-3248 will be administered orally once daily in 28-day cycles
|
Outcome Measures
Primary Outcome Measures
- 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
- 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)]
Eligibility Criteria
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
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Active, uncontrolled bacterial, fungal, or viral infection
-
Women who are lactating or breastfeeding, or pregnant
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UC San Diego Moores Cancer Center | La Jolla | California | United States | 92093 |
| 2 | Sarah Cannon Research Institute - Lake Nona | Orlando | Florida | United States | 32827 |
| 3 | START Midwest | Grand Rapids | Michigan | United States | 49546 |
| 4 | Sarah Cannon Research Institute | Nashville | Tennessee | United States | 37203 |
| 5 | Kaohsiung Medical University Hospital | Kaohsiung | Taiwan | 80756 |
Sponsors and Collaborators
- Kinnate Biopharma
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- KN-4802