A Study to Evaluate KIN-2787 in Participants With BRAF and/or NRAS Mutation Positive Solid Tumors

Phase 1

Recruiting

• Conditions: Participants with BRAF and/or NRAS mutation positive tumors
• Interventions: Drug: KIN-2787 and binimetinib; Drug: KIN-2787

• 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.

Study Timeline

• Study First Submitted: 2021-05-18
• Study First Submitted QC: 2021-05-28
• Study First Posted: 2021-06-04
• Study Start: 2021-08-04
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-27
• Last Update Posted: 2025-07-02
• Primary Completion: 2028-11-30
• Study Completion: 2029-03-30

Recruitment & Eligibility

• Status: 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

Group	Intervention	Description
Dose Escalation Combination therapy (Part A2)	KIN-2787 and binimetinib	Dose escalation of KIN-2787 and binimetinib
Dose Expansion Monotherapy (Part B1)	KIN-2787	Dose expansion evaluating the recommended phase 2 dose (RP2D) of KIN-2787
Dose Escalation Combination therapy (Part B2)	KIN-2787 and binimetinib	Dose expansion evaluating the recommended phase 2 dose (RP2D) of KIN-2787 and binimetinib
Dose Escalation Monotherapy (Part A1)	KIN-2787	Dose escalation of KIN-2787

Primary Outcome Measures

Name	Time	Method
Part A2 Dose Escalation: KIN-2787 + Binimetinib Combination	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 + 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

Name	Time	Method
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 (36)

The Angeles Clinic; 🇺🇸 Los Angeles, California, United States

UCLA; 🇺🇸 Los Angeles, California, United States

University of California San Diego, Moores Cancer Center; 🇺🇸 San Diego, California, United States

University of California San Francisco; 🇺🇸 San Francisco, California, United States

Stanford Cancer Center; 🇺🇸 Stanford, California, United States

Sarah Cannon Research Institute Denver; 🇺🇸 Denver, Colorado, United States

Sarah Cannon Research Institute - Florida Cancer Specialists; 🇺🇸 Orlando, Florida, United States

NYU Langone; 🇺🇸 New York, New York, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

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