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.
Study details:
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
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
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
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE1
Study ID
NCT04913285
Intervention or treatment
DRUG: KIN-2787
DRUG: KIN-2787 and binimetinib
Conditions
- Solid Tumor, Adult
- Non-small Cell Lung Cancer
- Melanoma
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Research sites nearby
Closest Location:
Calvary Mater Hospital Newcastle
Select from list below to view details:
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
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Who is running the clinical trial?
Pierre Fabre Medicament
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Dose Escalation Monotherapy (Part A1)
| Drug: KIN-2787 |
EXPERIMENTAL: Dose Escalation Combination therapy (Part A2)
| Drug: KIN-2787 and binimetinib |
EXPERIMENTAL: Dose Expansion Monotherapy (Part B1)
| Drug: KIN-2787 |
EXPERIMENTAL: Dose Escalation Combination therapy (Part B2)
| Drug: KIN-2787 and binimetinib |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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 | Initiation of study drug until disease progression (up to approximately 36 months) |
| In Part B (Dose Expansion) - disease control rate (DCR). | Not Specified | 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 | Initiation of study drug until disease progression (up to approximately 36 months) |
| In Part B (Dose Expansion) - duration of stable disease. | Not Specified | Initiation of study drug until disease progression (up to approximately 36 months) |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Part A1 Dose Escalation: Characterization of PK properties and effect of food on PK of KIN-2787 including, but not limited to tmax. | Not Specified | 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. | Not Specified | 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. | Not Specified | 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. | Not Specified | 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. | Not Specified | 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. | Not Specified | 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. | Not Specified | 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. | Not Specified | 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. | Not Specified | Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months) |
References
Clinical Trials Gov: A Study to Evaluate KIN-2787 in Participants With BRAF and/or NRAS Mutation Positive Solid TumorsOther trials to consider
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