Clinical trial NCT06800196: A Study of KNT-0916 in Treatment of Unresectable or Metastatic Solid Tumors with FGFR2 Alterations
Official title: A Phase I, Multicenter, Open-label Study to Evaluate the Safety, Pharmacokinetics, Preliminary Efficacy of KNT-0916 in Subjects with Unresectable or Metastatic Solid Tumors with FGFR2 Alterations
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Solid Tumors with FGFR2 Alterations, Adult
Lead sponsor: KinoTeck Therapeutics Co., Ltd
Sponsor class: INDUSTRY
First posted: 2025-01-29
Enrollment: 151
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed unresectable or metastatic solid tumor
* Documented FGFR2 gene fusion, mutation, or amplification per testing of blood and/or tumor
* Patient must have measurable disease per RECIST v1.1
* Patient has ECOG performance status of 0-1
* Patient must have disease that is refractory to standard therapy, disease that has not adequately responded to standard therapy, disease for which standard or curative therapy does not exist, or the patient must be intolerant to or have declined standard therapy
* An expected survival of ≥ 12 weeks.
* Adequate organ function, as measured by laboratory values

Exclusion Criteria:

* Prior treatment with any FGFR2 target therapy.
* Central nervous system metastasis with associated symptom and signs.
* Clinically significant, uncontrolled cardiovascular disease.
* History of interstitial lung disease, or infectious pneumonitis need heavy antibiotics therapy 5. As judged by the investigator, unsuitable for attending the study.

Primary outcomes:
measure: Dose-limiting Toxicity (DLT)
timeFrame: 4 weeks
measure: Maximum tolerated dose (MTD) or Maximum administered dose (MAD)
timeFrame: 12 months
measure: Incidence, relatedness, seriousness and severity of adverse events (AEs) per the National Cancer Institute Common Terminology Criteria for AE (NCI CTCAE) Version 5.0.
timeFrame: 33 months
measure: Recommended phase 2 dose (RP2D)
timeFrame: 33 months
Secondary outcomes:
measure: Objective response rate (ORR) assessed as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
timeFrame: 33 months
measure: Duration of response (DoR) assessed as per RECIST 1.1
timeFrame: 33 months
measure: Disease control rate (DCR) assessed as per RECIST 1.1
timeFrame: 33 months
measure: Progression-free survival (PFS) assessed as per RECIST 1.1
timeFrame: 33 months
measure: Overall survival (OS) assessed as per RECIST 1.1
timeFrame: 33 months
measure: Pharmacokinetic parameters including maximum plasma drug concentration (Cmax)
timeFrame: 33 months
measure: Pharmacokinetic parameters including area under the plasma concentration versus time curve (AUC)
timeFrame: 33 months
measure: Pharmacokinetic parameters including half-life (t1/2)
timeFrame: 33 months
measure: Pharmacokinetic parameters including time to maximum concentration (Tmax)
timeFrame: 33 months
measure: Pharmacokinetic parameters including Apparent clearance (CL/F)
timeFrame: 33 months
Other outcomes:
Locations:
Study officials:
affiliation: Sun Yat-sen University
name: Ruihua Xu
role: PRINCIPAL_INVESTIGATOR
References: