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
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Enrollment
- 151
- Locations
- 1
- Primary Endpoint
- Maximum tolerated dose (MTD) or Maximum administered dose (MAD)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
- •As judged by the investigator, unsuitable for attending the study.
Arms & Interventions
Part B - expansion
Oral dose of KNT-0916 as determined during Part A Dose Escalation.
Intervention: KNT-0916 (Drug)
Part A - dose escalation
Dose escalation of KNT-0916 in patients with advanced solid tumors.
Intervention: KNT-0916 (Drug)
Outcomes
Primary Outcomes
Maximum tolerated dose (MTD) or Maximum administered dose (MAD)
Time Frame: 12 months
Dose-limiting Toxicity (DLT)
Time Frame: 4 weeks
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
Secondary Outcomes
- Progression-free survival (PFS) assessed as per RECIST 1.1(33 months)
- Objective response rate (ORR) assessed as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1(33 months)
- Duration of response (DoR) assessed as per RECIST 1.1(33 months)
- Overall survival (OS) assessed as per RECIST 1.1(33 months)
- Pharmacokinetic parameters including maximum plasma drug concentration (Cmax)(33 months)
- Disease control rate (DCR) assessed as per RECIST 1.1(33 months)
- Pharmacokinetic parameters including area under the plasma concentration versus time curve (AUC)(33 months)
- Pharmacokinetic parameters including half-life (t1/2)(33 months)
- Pharmacokinetic parameters including time to maximum concentration (Tmax)(33 months)
- Pharmacokinetic parameters including Apparent clearance (CL/F)(33 months)