Melanoma, Non-small Cell Lung Cancer, Solid Tumor, Adult
Conditions
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
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.
Interventions
DRUGKIN-2787
KIN-2787 will be administered orally twice daily in 28-day cycles
DRUGKIN-2787 and binimetinib
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
Sponsors
Pierre Fabre Medicament
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) - 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 |
| In Part B (Dose Expansion) - disease control rate (DCR). | Initiation of study drug until disease progression (up to approximately 36 months) | — |
| 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. |
| 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) - 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
| Measure | Time frame |
|---|---|
| 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 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 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 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) |
| 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) |
| 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) |
Countries
Australia, China, France, Italy, Spain, Taiwan, United States
Contacts
CONTACTData Protection Officer
STUDY_CHAIRData Protection Officer
Pierre Fabre Laboratories
Outcome results
None listed