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NCT Number: NCT04913285

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

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.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Solid Tumor, Adult Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Endocrine System Diseases Lung Diseases Lung Neoplasms Melanoma Neoplasm Metastasis Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Neoplastic Processes Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Non-small Cell Lung Cancer Pathologic Processes Pathological Conditions, Signs and Symptoms Respiratory Tract Diseases Respiratory Tract Neoplasms Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases Thoracic Neoplasms Thyroid Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Calvary Mater Hospital Newcastle, Waratah, New South Wales, Australia

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

KIN-2787

Drug

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

Other names: exarafenib

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

Other names: exarafenib and binimetinib

Primary outcomes

  1. Part A1 Dose escalation monotherapy:

    Time frame: 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.

  2. Part A2 Dose Escalation: KIN-2787 + Binimetinib Combination

    Time frame: 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.

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

    Time frame: 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

  4. In Part B (Dose Expansion) - disease control rate (DCR).

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

  5. In Part B (Dose Expansion) - duration of overall response (DOR).

    Time frame: 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

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

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

Secondary outcomes

  1. Part A1 Dose Escalation: Characterization of PK properties and effect of food on PK of KIN-2787 including, but not limited to tmax.

    Time frame: Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)

  2. Part A1 Dose Escalation: Characterization of PK properties and effect of food on PK of KIN-2787 including, but not limited to AUC.

    Time frame: Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)

  3. Part A1 Dose Escalation: Characterization of PK properties and effect of food on PK of KIN-2787 including, but not limited to Cmax.

    Time frame: Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)

  4. Part A2 Dose Escalation: characterization of PK properties of KIN-2787 and binimetinib in combination including, but not limited to Cmax.

    Time frame: Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)

  5. Part A2 Dose Escalation: characterization of PK properties of KIN-2787 and binimetinib in combination including, but not limited to AUC.

    Time frame: Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)

  6. Part A2 Dose Escalation: characterization of PK properties of KIN-2787 and binimetinib in combination including, but not limited to tmax.

    Time frame: Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)

  7. Part B Dose Expansion: characterization of PK properties of KIN-2787, and for (B2) KIN-2787 + binimetinib including, but not limited to AUC.

    Time frame: Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)

  8. Part B Dose Expansion: characterization of PK properties of KIN-2787, and for (B2) KIN-2787 + binimetinib including, but not limited to Cmax.

    Time frame: Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)

  9. Part B Dose Expansion: characterization of PK properties of KIN-2787, and for (B2) KIN-2787 + binimetinib including, but not limited to tmax.

    Time frame: Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)

Sponsors and collaborators

Lead sponsor

Pierre Fabre Medicament

Industry

Registry information

Official study title

A Phase 1/1b Open-label, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of KIN-2787 in Participants With BRAF and/or NRAS Mutation-positive Solid Tumors.

Important dates

Study start
2021
Primary completion
2028
Study completion
2029
First posted
Jun 4, 2021
Registry last updated
Apr 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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