What is the Purpose of this Study?
2. Study Objectives 2.1. Part A Dose Escalation 2.1.1. Part A1: KIN-2787 Monotherapy Dose Escalation -The primary objectives of Part A1 are to determine the safety and tolerability of PO administration of KIN-2787 including DLTs in participants with BRAF mutation-positive advanced or metastatic solid tumors or melanoma harboring an NRAS mutation, and to identify the MTD and/or the appropriate dose for further clinical investigation in Part B1 Dose Expansion. -Secondary objectives include characterization of PK properties and effect of food on PK of KIN-2787. -Exploratory objectives include additional characterization of KIN-2787 PK, effect of KIN-2787 on survival and other time-to-event endpoints, estimation of PD effects of KIN-2787 in blood samples and tumor biopsies, assessment of both genotype and genotypic changes under treatment to outcome. 2.1.2. Part A2: KIN-2787 Plus Binimetinib Combination Dose Escalation -The primary objectives of Part A2 are to determine the safety and tolerability of PO administration of KIN-2787 + binimetinib including DLTs in participants with oncogenic BRAF or NRAS mutation-positive advanced or metastatic solid tumors, and to identify the MTD and/or 1 or 2 RP2D for further clinical investigation. -The secondary objective is characterization of PK properties of KIN-2787 and binimetinib in combination. -Exploratory objectives include additional characterization of KIN-2787 PK, effect of KIN-2787 on survival, and other time-to-event endpoints, estimation of PD effects of KIN-2787 in blood samples and tumor biopsies, assessment of both genotype and genotypic changes under treatment to outcome. 2.2. Part B1: KIN-2787 Monotherapy Dose Expansion -The primary objective of the Part B1 Monotherapy Dose Expansion portion of the study is to assess preliminary evidence of the anti-cancer activity of KIN-2787 in participants with advanced or metastatic solid cancers and NRAS mutation-positive melanoma that harbor any oncogenic BRAF or NRAS genomic alteration. -The secondary objective is to further evaluate the safety, tolerability, and the PK characteristics of KIN-2787 at the RP2D. -Exploratory objectives include additional characterization of KIN-2787 PK, effect of KIN-2787 on survival and other time-to-event endpoints, estimation of PD effects of KIN-2787 in blood samples and tumor biopsies, assessment of both genotype and genotypic changes under treatment to outcome, evaluation of the PK of a new KIN-2787 tablet F2 formulation, impact on patient-reported outcome (PRO) measures. 2.3. Part B2: KIN-2787 Plus Binimetinib Combination Dose Expansion -The primary objective of the Part B2 Combination Dose Expansion portion of the study is to evaluate preliminary evidence of the anti-cancer activity of KIN-2787 + binimetinib for tumors with NRAS Q61, G12, and G13 positive and oncogenic BRAF Class II mutations for one or more RP2D based on the results of Part A2. -The secondary objective is to further evaluate the safety, tolerability, and the PK characteristics of KIN-2787 + binimetinib at the RP2D. -The exploratory objectives include additional characterization of KIN-2787 + binimetinib PK, effect of KIN-2787+binimetinib on survival and other time-to-event endpoints, estimation of PD effects of KIN-2787+binimetinib in blood samples and tumor biopsies, assessment of both genotype and genotypic changes under treatment to outcome and impact of PRO measures.
Eligibility
- * 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.
Where can I participate?
CS Cancer at The Angeles Clinic and Research Institute : Saba Mukarram
More about this Clinical Trial
What is the full name of this clinical trial?
KN-8701/KIN2787CI101: 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