Clinical trial NCT04913285: A Study to Evaluate KIN-2787 in Participants with BRAF And/or NRAS Mutation Positive Solid Tumors
Official 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
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
Lead sponsor: Pierre Fabre Medicament
Sponsor class: INDUSTRY
First posted: 2021-06-04
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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: 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.

Primary outcomes:
measure: Part A1 Dose escalation monotherapy:
timeFrame: Initiation of study drug through 28 days after last dose (up to approximately 18 months)
measure: Part A2 Dose Escalation: KIN-2787 + Binimetinib Combination
timeFrame: Initiation of study drug through 28 days after last dose (up to approximately 18 months)
measure: In Part B (Dose Expansion) - objective response rate (ORR) using RECIST v1.1.
timeFrame: Initiation of study drug until disease progression (up to approximately 36 months)
measure: In Part B (Dose Expansion) - disease control rate (DCR).
timeFrame: Initiation of study drug until disease progression (up to approximately 36 months)
measure: In Part B (Dose Expansion) - duration of overall response (DOR).
timeFrame: Initiation of study drug until disease progression (up to approximately 36 months)
measure: In Part B (Dose Expansion) - duration of stable disease.
timeFrame: Initiation of study drug until disease progression (up to approximately 36 months)
Secondary outcomes:
measure: Part A1 Dose Escalation: Characterization of PK properties and effect of food on PK of KIN-2787 including, but not limited to tmax.
timeFrame: Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)
measure: Part A1 Dose Escalation: Characterization of PK properties and effect of food on PK of KIN-2787 including, but not limited to AUC.
timeFrame: Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)
measure: Part A1 Dose Escalation: Characterization of PK properties and effect of food on PK of KIN-2787 including, but not limited to Cmax.
timeFrame: Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)
measure: Part A2 Dose Escalation: characterization of PK properties of KIN-2787 and binimetinib in combination including, but not limited to Cmax.
timeFrame: Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)
measure: Part A2 Dose Escalation: characterization of PK properties of KIN-2787 and binimetinib in combination including, but not limited to AUC.
timeFrame: Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)
measure: Part A2 Dose Escalation: characterization of PK properties of KIN-2787 and binimetinib in combination including, but not limited to tmax.
timeFrame: Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)
measure: Part B Dose Expansion: characterization of PK properties of KIN-2787, and for (B2) KIN-2787 + binimetinib including, but not limited to AUC.
timeFrame: Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)
measure: Part B Dose Expansion: characterization of PK properties of KIN-2787, and for (B2) KIN-2787 + binimetinib including, but not limited to Cmax.
timeFrame: Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)
measure: Part B Dose Expansion: characterization of PK properties of KIN-2787, and for (B2) KIN-2787 + binimetinib including, but not limited to tmax.
timeFrame: Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UCSD Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institute Denver
state: Colorado
city: Orlando
country: United States
facility: Sarah Cannon Research Institute - Florida Cancer Specialists
state: Florida
city: New York
country: United States
facility: NYU Langone
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Nashville
country: United States
facility: Sarah Cannon Research Institute-Tennessee Oncology
state: Tennessee
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Waratah
country: Australia
facility: Calvary Mater Hospital Newcastle
state: New South Wales
city: Wollstonecraft
country: Australia
facility: Melanoma Institute Australia
state: New South Wales
city: Southport
country: Australia
facility: Tasman Health Care
state: Queensland
city: Perth
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Harbin City
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Linyi
country: China
facility: Linyi Cancer Hospital
state: Shandong
city: Beijing
country: China
facility: Beijing University Cancer Hospital
city: Shanghai
country: China
facility: The Shanghai Pulmonary Hospital
city: Bordeaux
country: France
facility: Institut Bergonie
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: APHM-CHU La Timone
city: Nantes
country: France
facility: CHU Nantes-Hotel Dieu
city: Villejuif
country: France
facility: Gustave Roussy
city: Barcelona
country: Spain
facility: Hospital Quiron Dexeus
city: Las Palmas De Gran Canaria
country: Spain
facility: Hospital Universitario Insular de Gran Canaria
city: Madrid
country: Spain
facility: START Madrid
city: Madrid
country: Spain
facility: Hospital General Gregorio Marañón
city: Valencia
country: Spain
facility: INCLIVA (Hospital Clinico de Valencia)
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: Pierre Fabre Laboratories
name: CLaire FABRE, MD
role: STUDY_CHAIR
References: