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NCT04913285PHASE1Recruiting

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

Pierre Fabre Medicament

Start Date

8/4/2021

Completion Date

3/30/2029

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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 Complete inclusion and exclusion criteria are listed in the clinical study protocol.

Interventions

DRUG

KIN-2787

DRUG

KIN-2787 and binimetinib

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Conditions

Solid Tumor, AdultNon-small Cell Lung CancerMelanoma

Locations

The Angeles Clinic

Los Angeles, California 90025-6602

United States

UCLA

Los Angeles, California 90095

United States

University of California San Diego, Moores Cancer Center

San Diego, California 92093

United States

University of California San Francisco

San Francisco, California 94143-2205

United States

Sarah Cannon Research Institute Denver

Denver, Colorado 80218-1238

United States

Mayo Clinic - Florida

Jacksonville, Florida 32224

United States

Sarah Cannon Research Institute - Florida Cancer Specialists

Orlando, Florida 32827

United States

Mayo Clinic - Rochester

Rochester, Minnesota 55905

United States

Atlantic Health

Morristown, New Jersey 07960

United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey 08901

United States

NYU Langone

New York, New York 10016

United States

Cleveland Clinic

Cleveland, Ohio 44195

United States

Sarah Cannon Research Institute-Tennessee Oncology

Nashville, Tennessee 37203

United States

MD Anderson

Houston, Texas 77030

United States

Virginia Cancer Specialists

Fairfax, Virginia 22031

United States

Calvary Mater Hospital Newcastle

Waratah, New South Wales 2298

Australia

Melanoma Institute Australia

Wollstonecraft, New South Wales 2065

Australia

Tasman Health Care

Southport, Queensland 4215

Australia

Austin Health

Heidelberg, Victoria 3084

Australia

Linear Clinical Research

Perth, Western Australia 6009

Australia

Harbin Medical University Cancer Hospital

Haerbin, Heilongjiang 150081

China

Linyi Cancer Hospital

Linyi, Shandong 276001

China

Beijing University Cancer Hospital

Beijing, 100142

China

The Shanghai Pulmonary Hospital

Shanghai, 200433

China

Institut Bergonie

Bordeaux,

France

Centre Francois Baclesse

Caen,

France

CHU de Lille

Lille,

France

Centre Leon Berard

Lyon,

France

APHM-CHU La Timone

Marseille,

France

CHU Nantes-Hotel Dieu

Nantes,

France

CHU de Nice - Hôpital Archet 2

Nice,

France

APHP - Hôpital St Louis

Paris,

France

Hospices Civiles de Lyon - Hôpital Lyon Sud

Pierre-Bénite,

France

CHU de Poitiers

Poitiers,

France

Oncopole Claudius Regaud

Toulouse, 31059

France

Gustave Roussy

Villejuif, 94805

France

Istituto Nazionale dei Tumori Fondazione G. Pascale

Naples, 80131

Italy

Arance

Barcelona, Spain

Spain

NEXT Quirónsalud Madrid

Madrid, Spain

Spain

H. Regional de Málaga

Málaga, Spain

Spain

H. Virgen Macarena

Seville, Spain

Spain

Berrocal

Valencia, Spain

Spain

Hospital Quiron Dexeus

Barcelona,

Spain

Hospital Universitario Insular de Gran Canaria

Las Palmas de Gran Canaria,

Spain

START Madrid

Madrid, 28050

Spain

Hospital General Gregorio Marañón

Madrid, 29009

Spain

INCLIVA (Hospital Clinico de Valencia)

Valencia,

Spain

National Taiwan University Hospital

Taipei,

Taiwan