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

Phase 1Active Not RecruitingNCT04913285

Pierre Fabre Medicament400 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

400

Conditions

Solid Tumor, Adult Non-small Cell Lung Cancer Melanoma

Interventions

KIN-2787DRUG

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

KIN-2787 and binimetinibDRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (50)

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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

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

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

Time frame: 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

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

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

Data from ClinicalTrials.gov

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Sarah Cannon Research Institute - Florida Cancer Specialists

Orlando, Florida, United States

Mayo Clinic - Rochester

Rochester, Minnesota, United States

Atlantic Health

Morristown, New Jersey, United States

...and 40 more locations

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