A Study to Evaluate KIN-2787 in Participants with BRAF And/or NRAS Mutation Positive Solid Tumors
- Conditions
- Solid Tumor, AdultNon-small Cell Lung CancerMelanoma
- Interventions
- Registration Number
- NCT04913285
- Lead Sponsor
- Pierre Fabre Medicament
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 400
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation Combination therapy (Part A2) KIN-2787 and binimetinib Dose escalation of KIN-2787 and binimetinib Dose Expansion Monotherapy (Part B1) KIN-2787 Dose expansion evaluating the recommended phase 2 dose (RP2D) of KIN-2787 Dose Escalation Combination therapy (Part B2) KIN-2787 and binimetinib Dose expansion evaluating the recommended phase 2 dose (RP2D) of KIN-2787 and binimetinib Dose Escalation Monotherapy (Part A1) KIN-2787 Dose escalation of KIN-2787
- Primary Outcome Measures
Name Time Method Part A2 Dose Escalation: KIN-2787 + Binimetinib Combination 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.
In Part B (Dose Expansion) - duration of overall response (DOR). 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
Part A1 Dose escalation monotherapy: 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.
In Part B (Dose Expansion) - duration of stable disease. 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) - objective response rate (ORR) using RECIST v1.1. 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
- Secondary Outcome Measures
Name Time Method 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 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 B Dose Expansion: characterization of PK properties of KIN-2787, and for (B2) KIN-2787 + binimetinib 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 B Dose Expansion: characterization of PK properties of KIN-2787, and for (B2) KIN-2787 + binimetinib 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 A2 Dose Escalation: characterization of PK properties of KIN-2787 and binimetinib in combination 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 tmax. 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) Part B Dose Expansion: characterization of PK properties of KIN-2787, and for (B2) KIN-2787 + binimetinib including, but not limited to Cmax. Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)
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Trial Locations
- Locations (29)
APHM-CHU La Timone
🇫🇷Marseille, France
UCSD Moores Cancer Center
🇺🇸La Jolla, California, United States
UCLA
🇺🇸Los Angeles, California, United States
Harbin Medical University Cancer Hospital
🇨🇳Harbin City, Heilongjiang, China
Linyi Cancer Hospital
🇨🇳Linyi, Shandong, China
Beijing University Cancer Hospital
🇨🇳Beijing, China
The Shanghai Pulmonary Hospital
🇨🇳Shanghai, China
Institut Bergonie
🇫🇷Bordeaux, France
Centre Leon Berard
🇫🇷Lyon, France
CHU Nantes-Hotel Dieu
🇫🇷Nantes, France
Gustave Roussy
🇫🇷Villejuif, France
Hospital Quiron Dexeus
🇪🇸Barcelona, Spain
START Madrid
🇪🇸Madrid, Spain
Hospital General Gregorio Marañón
🇪🇸Madrid, Spain
INCLIVA (Hospital Clinico de Valencia)
🇪🇸Valencia, Spain
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Stanford Cancer Center
🇺🇸Stanford, California, United States
Sarah Cannon Research Institute Denver
🇺🇸Denver, Colorado, United States
Sarah Cannon Research Institute - Florida Cancer Specialists
🇺🇸Orlando, Florida, United States
NYU Langone
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Sarah Cannon Research Institute-Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Calvary Mater Hospital Newcastle
🇦🇺Waratah, New South Wales, Australia
Melanoma Institute Australia
🇦🇺Wollstonecraft, New South Wales, Australia
Tasman Health Care
🇦🇺Southport, Queensland, Australia
Linear Clinical Research
🇦🇺Perth, Western Australia, Australia
Hospital Universitario Insular de Gran Canaria
🇪🇸Las Palmas De Gran Canaria, Spain