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

NCT ID: NCT04913285

Last Updated: 2025-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

400 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-08-04

Study Completion Date

2029-03-30

Brief Summary

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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

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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.

Conditions

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Solid Tumor, Adult Non-small Cell Lung Cancer Melanoma

Keywords

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BRAF inhibitor BRAF pan-RAF pan-RAF inhibitor RAF1 ARAF BRAF alteration BRAF Class II BRAF Class III V600 tumor growth inhibitor (TGI) melanoma NSCLC solid tumor targeted therapy BRAF Class I NRAS Metastatic Unresectable CRC ATC Colon Thyroid Advanced Exarafenib binimetinib

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose Escalation Monotherapy (Part A1)

Dose escalation of KIN-2787

Group Type EXPERIMENTAL

KIN-2787

Intervention Type DRUG

KIN-2787 will be administered orally twice daily in 28-day cycles

Dose Escalation Combination therapy (Part A2)

Dose escalation of KIN-2787 and binimetinib

Group Type EXPERIMENTAL

KIN-2787 and binimetinib

Intervention Type DRUG

Continuous and Ramp-Up cohorts: KIN-2787 (exarafenib) and binimetinib will be administered orally twice daily in 28-day cycles Intermittent Cohort: KIN-2787 will be administered orally twice daily and binimetinib will be administered twice daily for 5 days on, 2 days off for 28-day cycles

Dose Expansion Monotherapy (Part B1)

Dose expansion evaluating the recommended phase 2 dose (RP2D) of KIN-2787

Group Type EXPERIMENTAL

KIN-2787

Intervention Type DRUG

KIN-2787 will be administered orally twice daily in 28-day cycles

Dose Escalation Combination therapy (Part B2)

Dose expansion evaluating the recommended phase 2 dose (RP2D) of KIN-2787 and binimetinib

Group Type EXPERIMENTAL

KIN-2787 and binimetinib

Intervention Type DRUG

Continuous and Ramp-Up cohorts: KIN-2787 (exarafenib) and binimetinib will be administered orally twice daily in 28-day cycles Intermittent Cohort: KIN-2787 will be administered orally twice daily and binimetinib will be administered twice daily for 5 days on, 2 days off for 28-day cycles

Interventions

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KIN-2787

KIN-2787 will be administered orally twice daily in 28-day cycles

Intervention Type DRUG

KIN-2787 and binimetinib

Continuous and Ramp-Up cohorts: KIN-2787 (exarafenib) and binimetinib will be administered orally twice daily in 28-day cycles Intermittent Cohort: KIN-2787 will be administered orally twice daily and binimetinib will be administered twice daily for 5 days on, 2 days off for 28-day cycles

Intervention Type DRUG

Other Intervention Names

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exarafenib exarafenib and binimetinib

Eligibility Criteria

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Inclusion Criteria

* Provide written informed consent prior to initiation of any study-specific procedures.
* Metastatic or advanced stage solid tumor
* Known BRAF Class I, Class II, or Class III alteration or melanoma with an NRAS mutation as confirmed by previous genomic analysis of tumor tissue or ctDNA.
* Measurable (Part A and B) or evaluable (Part A only) disease by RECIST v1.1.
* ECOG performance status 0-1
* Adequate organ function, as measured by laboratory values (criteria listed in protocol).
* Able to swallow, retain, and absorb oral medications.

Exclusion Criteria

* Known participants who have received local therapy with either surgery and/or radiation therapy (participants with asymptomatic untreated brain metastasis may be eligible if met with certain criteria)
* In Part B Dose Expansion, previous treatment with any approved or in-development small molecule BRAF-, MEK-, or MAPK-directed inhibitor therapy.
* GI tract disease causing an inability to take oral medication, malabsorption syndrome, requirement for intravenous alimentation, or uncontrolled inflammatory GI disease.
* Active, uncontrolled bacterial, fungal, or viral infection.
* Participant with a positive test result for SARS-CoV2 infection, is known to have asymptomatic infection or is suspected of having SARS-CoV2, is excluded
* Women who are lactating or breastfeeding, or pregnant.
* Participants with any other active treated malignancy within 3 years prior to enrollment
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pierre Fabre Medicament

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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CLaire FABRE, MD

Role: STUDY_CHAIR

Pierre Fabre Laboratories

Locations

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The Angeles Clinic

Los Angeles, California, United States

Site Status

UCLA

Los Angeles, California, United States

Site Status

University of California San Diego, Moores Cancer Center

San Diego, California, United States

Site Status

University of California San Francisco

San Francisco, California, United States

Site Status

Stanford Cancer Center

Stanford, California, United States

Site Status

Sarah Cannon Research Institute Denver

Denver, Colorado, United States

Site Status

Mayo Clinic - Florida

Jacksonville, Florida, United States

Site Status

Sarah Cannon Research Institute - Florida Cancer Specialists

Orlando, Florida, United States

Site Status

Mayo Clinic - Rochester

Rochester, Minnesota, United States

Site Status

Atlantic Health

Morristown, New Jersey, United States

Site Status

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Site Status

NYU Langone

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Sarah Cannon Research Institute-Tennessee Oncology

Nashville, Tennessee, United States

Site Status

MD Anderson

Houston, Texas, United States

Site Status

Virginia Cancer Specialists

Fairfax, Virginia, United States

Site Status

Calvary Mater Hospital Newcastle

Waratah, New South Wales, Australia

Site Status

Melanoma Institute Australia

Wollstonecraft, New South Wales, Australia

Site Status

Tasman Health Care

Southport, Queensland, Australia

Site Status

Austin Health

Heidelberg, Victoria, Australia

Site Status

Linear Clinical Research

Perth, Western Australia, Australia

Site Status

Harbin Medical University Cancer Hospital

Haerbin, Heilongjiang, China

Site Status

Linyi Cancer Hospital

Linyi, Shandong, China

Site Status

Beijing University Cancer Hospital

Beijing, , China

Site Status

The Shanghai Pulmonary Hospital

Shanghai, , China

Site Status

Institut Bergonie

Bordeaux, , France

Site Status

Centre Francois Baclesse

Caen, , France

Site Status

CHU de Lille

Lille, , France

Site Status

Centre Leon Berard

Lyon, , France

Site Status

APHM-CHU La Timone

Marseille, , France

Site Status

CHU Nantes-Hotel Dieu

Nantes, , France

Site Status

CHU de Nice - Hôpital Archet 2

Nice, , France

Site Status

APHP - Hôpital St Louis

Paris, , France

Site Status

Hospices Civiles de Lyon - Hôpital Lyon Sud

Pierre-Bénite, , France

Site Status

CHU de Poitiers

Poitiers, , France

Site Status

Oncopole Claudius Regaud

Toulouse, , France

Site Status

Gustave Roussy

Villejuif, , France

Site Status

Istituto Nazionale dei Tumori Fondazione G. Pascale

Napoli, , Italy

Site Status

Arance

Barcelona, Spain, Spain

Site Status

NEXT Quirónsalud Madrid

Madrid, Spain, Spain

Site Status

H. Regional de Málaga

Málaga, Spain, Spain

Site Status

H. Virgen Macarena

Seville, Spain, Spain

Site Status

Berrocal

Valencia, Spain, Spain

Site Status

Hospital Quiron Dexeus

Barcelona, , Spain

Site Status

Hospital Universitario Insular de Gran Canaria

Las Palmas de Gran Canaria, , Spain

Site Status

START Madrid

Madrid, , Spain

Site Status

Hospital General Gregorio Marañón

Madrid, , Spain

Site Status

INCLIVA (Hospital Clinico de Valencia)

Valencia, , Spain

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Countries

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Netherlands South Korea United States Australia China France Italy Spain Taiwan

Other Identifiers

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KIN 2787CI101

Identifier Type: OTHER

Identifier Source: secondary_id

KN-8701

Identifier Type: -

Identifier Source: org_study_id