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A clinical study to learn about the safety and effects of KIN-2787, a new oral anticancer drug for the treatment of patients with BRAF and/or NRAS Mutation-positive Solid Tumors

Phase 1
Recruiting
Conditions
Participants with BRAF and/or NRAS mutation positive tumors
Interventions
Registration Number
2024-516331-27-00
Lead Sponsor
Pierre Fabre Medicament
Brief Summary

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of KIN-2787 in adults with BRAF/NRAS-mutated advanced or metastatic solid tumors.

Detailed Description

This is a two-part, open-label, multi-center, dose escalation and dose expansion study in participants with BRAF mutation-positive and/or NRAS mutation-positive tumors designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of KIN-2787, a RAF small molecule kinase inhibitor, to determine a recommended Phase 2 dose (RP2D) of KIN-2787, and to assess the objective response to KIN-2787 therapy alone and in combination with binimetinib, a mitogen-activated protein kinase (MEK) inhibitor.

The dose expansion phase (Part B) will assess the safety and efficacy of KIN-2787 at the recommended dose and schedule in patients with cancers that contain BRAF Class I, II or III mutations, including lung cancer, melanoma, and other selected solid tumors.

Recruitment & Eligibility

Status
Ongoing, recruiting
Sex
Not specified
Target Recruitment
199
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Dose Escalation Combination therapy (Part A2)KIN-2787 and binimetinibDose escalation of KIN-2787 and binimetinib
Dose Expansion Monotherapy (Part B1)KIN-2787Dose expansion evaluating the recommended phase 2 dose (RP2D) of KIN-2787
Dose Escalation Combination therapy (Part B2)KIN-2787 and binimetinibDose expansion evaluating the recommended phase 2 dose (RP2D) of KIN-2787 and binimetinib
Dose Escalation Monotherapy (Part A1)KIN-2787Dose escalation of KIN-2787
Primary Outcome Measures
NameTimeMethod
Part A2 Dose Escalation: KIN-2787 + Binimetinib CombinationInitiation of study drug through 28 days after last dose (up to approximately 18 months)

To determine the safety and tolerability of oral administration of KIN-2787 + binimetinib including DLTs, and to identify the MTD and/or the appropriate dose for further clinical investigation.

In Part B (Dose Expansion) - duration of overall response (DOR).Initiation of study drug until disease progression (up to approximately 36 months)

Measure of clinical benefit, defined as the time from initial tumor response to documented tumor progression

Part A1 Dose escalation monotherapy:Initiation of study drug through 28 days after last dose (up to approximately 18 months)

To determine the safety and tolerability of oral administration of KIN-2787 including dose-limiting toxicities (DLTs), and to identify the maximum tolerated dose (MTD) and/or the appropriate dose for further clinical investigation in Part B Dose Expansion.

In Part B (Dose Expansion) - duration of stable disease.Initiation of study drug until disease progression (up to approximately 36 months)
In Part B (Dose Expansion) - disease control rate (DCR).Initiation of study drug until disease progression (up to approximately 36 months)
In Part B (Dose Expansion) - objective response rate (ORR) using RECIST v1.1.Initiation of study drug until disease progression (up to approximately 36 months)

To assess preliminary evidence of the anti-cancer activity of KIN-2787 and for (B2) KIN-2787 + binimetinib

Secondary Outcome Measures
NameTimeMethod
Part A1 Dose Escalation: Characterization of PK properties and effect of food on PK of KIN-2787 including, but not limited to Cmax.Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)
Part A1 Dose Escalation: Characterization of PK properties and effect of food on PK of KIN-2787 including, but not limited to AUC.Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)
Part B Dose Expansion: characterization of PK properties of KIN-2787, and for (B2) KIN-2787 + binimetinib including, but not limited to AUC.Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)
Part B Dose Expansion: characterization of PK properties of KIN-2787, and for (B2) KIN-2787 + binimetinib including, but not limited to tmax.Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)
Part A2 Dose Escalation: characterization of PK properties of KIN-2787 and binimetinib in combination including, but not limited to tmax.Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)
Part A1 Dose Escalation: Characterization of PK properties and effect of food on PK of KIN-2787 including, but not limited to tmax.Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)
Part A2 Dose Escalation: characterization of PK properties of KIN-2787 and binimetinib in combination including, but not limited to Cmax.Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)
Part A2 Dose Escalation: characterization of PK properties of KIN-2787 and binimetinib in combination including, but not limited to AUC.Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)
Part B Dose Expansion: characterization of PK properties of KIN-2787, and for (B2) KIN-2787 + binimetinib including, but not limited to Cmax.Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)

Trial Locations

Locations (24)

Hospital Universitario Regional De Malaga

🇪🇸

Malaga, Spain

Hospital Clinic De Barcelona

🇪🇸

Barcelona, Spain

Hospital General Universitario Gregorio Maranon

🇪🇸

Madrid, Spain

Hospital Clinico Universitario De Valencia

🇪🇸

Valencia, Spain

Hospital Universitario Quironsalud Madrid

🇪🇸

Pozuelo De Alarcon, Spain

Hospital Universitario Virgen De La Macarena

🇪🇸

Sevilla, Spain

Complejo Hospitalario Universitario Insular Materno Infantil

🇪🇸

Las Palmas De Gran Canaria, Spain

Hospital General Universitario De Valencia

🇪🇸

Valencia, Spain

Hospital Universitario Hm Sanchinarro

🇪🇸

Madrid, Spain

Hospital Universitari Dexeus Grupo Quironsalud

🇪🇸

Barcelona, Spain

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Hospital Universitario Regional De Malaga
🇪🇸Malaga, Spain
Miguel Ángel Berciano Guerrero
Site contact
0034608093004
migueberci@gmail.com
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