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

NCT04913285 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: KN-8701KIN 2787CI101
• Study Type: interventional
• Target: 400
• Locations: 7 countries
• Sites: 50

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.

Conditions

Solid Tumor, Adult; Non-small Cell Lung Cancer; Melanoma

Keywords

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

Outcome Measures

Primary Outcomes (6)

• Part A1 Dose escalation monotherapy:

  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.

  Initiation of study drug through 28 days after last dose (up to approximately 18 months)

• Part A2 Dose Escalation: KIN-2787 + Binimetinib Combination

  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.

  Initiation of study drug through 28 days after last dose (up to approximately 18 months)

• In Part B (Dose Expansion) - objective response rate (ORR) using RECIST v1.1.

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

  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) - duration of overall response (DOR).

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

  Initiation of study drug until disease progression (up to approximately 36 months)

• In Part B (Dose Expansion) - duration of stable disease.

  Initiation of study drug until disease progression (up to approximately 36 months)

Secondary Outcomes (9)

• 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 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 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 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)

Study Arms (4)

Dose Escalation Monotherapy (Part A1)

EXPERIMENTAL

Dose escalation of KIN-2787

Drug: KIN-2787

Dose Escalation Combination therapy (Part A2)

EXPERIMENTAL

Dose escalation of KIN-2787 and binimetinib

Drug: KIN-2787 and binimetinib

Dose Expansion Monotherapy (Part B1)

EXPERIMENTAL

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

Drug: KIN-2787

Dose Escalation Combination therapy (Part B2)

EXPERIMENTAL

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

Drug: KIN-2787 and binimetinib

Interventions

KIN-2787 DRUG

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

Also known as: exarafenib

Dose Escalation Monotherapy (Part A1); Dose Expansion Monotherapy (Part B1)

KIN-2787 and binimetinib 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

Also known as: exarafenib and binimetinib

Dose Escalation Combination therapy (Part A2); Dose Escalation Combination therapy (Part B2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Pierre Fabre Medicament: lead

Study Sites (50)

The Angeles Clinic

Los Angeles, California, 90025-6602, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

University of California San Diego, Moores Cancer Center

San Diego, California, 92093, United States

Location

University of California San Francisco

San Francisco, California, 94143-2205, United States

Location

Stanford Cancer Center

Stanford, California, 94305, United States

Location

Sarah Cannon Research Institute Denver

Denver, Colorado, 80218-1238, United States

Location

Mayo Clinic - Florida

Jacksonville, Florida, 32224, United States

Location

Sarah Cannon Research Institute - Florida Cancer Specialists

Orlando, Florida, 32827, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Atlantic Health

Morristown, New Jersey, 07960, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

NYU Langone

New York, New York, 10016, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Sarah Cannon Research Institute-Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Calvary Mater Hospital Newcastle

Waratah, New South Wales, 2298, Australia

Location

Melanoma Institute Australia

Wollstonecraft, New South Wales, 2065, Australia

Location

Tasman Health Care

Southport, Queensland, 4215, Australia

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

Linear Clinical Research

Perth, Western Australia, 6009, Australia

Location

Harbin Medical University Cancer Hospital

Haerbin, Heilongjiang, 150081, China

Location

Linyi Cancer Hospital

Linyi, Shandong, 276001, China

Location

Beijing University Cancer Hospital

Beijing, 100142, China

Location

The Shanghai Pulmonary Hospital

Shanghai, 200433, China

Location

Institut Bergonie

Bordeaux, France

Location

Centre Francois Baclesse

Caen, France

Location

CHU de Lille

Lille, France

Location

Centre Leon Berard

Lyon, France

Location

APHM-CHU La Timone

Marseille, France

Location

CHU Nantes-Hotel Dieu

Nantes, France

Location

CHU de Nice - Hôpital Archet 2

Nice, France

Location

APHP - Hôpital St Louis

Paris, France

Location

Hospices Civiles de Lyon - Hôpital Lyon Sud

Pierre-Bénite, France

Location

CHU de Poitiers

Poitiers, France

Location

Oncopole Claudius Regaud

Toulouse, 31059, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Istituto Nazionale dei Tumori Fondazione G. Pascale

Naples, 80131, Italy

Location

Arance

Barcelona, Spain, Spain

Location

NEXT Quirónsalud Madrid

Madrid, Spain, Spain

Location

H. Regional de Málaga

Málaga, Spain, Spain

Location

H. Virgen Macarena

Seville, Spain, Spain

Location

Berrocal

Valencia, Spain, Spain

Location

Hospital Quiron Dexeus

Barcelona, Spain

Location

Hospital Universitario Insular de Gran Canaria

Las Palmas de Gran Canaria, Spain

Location

START Madrid

Madrid, 28050, Spain

Location

Hospital General Gregorio Marañón

Madrid, 29009, Spain

Location

INCLIVA (Hospital Clinico de Valencia)

Valencia, Spain

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Melanoma; Neoplasm Metastasis; Thyroid Diseases

Interventions

binimetinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Endocrine System Diseases

Study Officials

• Grazia Saturno, PhD

  Pierre Fabre Laboratories

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2021
• First Posted: June 4, 2021
• Study Start: August 4, 2021
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): March 30, 2029
• Last Updated: April 27, 2026

Record last verified: 2025-12

Locations

AU (5); IT (1); ES (10); US (17); CN (4); FR (12); TW (1)