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
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.
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
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.
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.
- Rutgers University
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.
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site ClinicalTrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
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