A Study to Evaluate KIN-2787 in Participants With BRAF and/or NRAS Mutation Positive Solid Tumors

Non-small Cell Lung Cancer Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04913285
• Other study ID #: KN-8701
• Secondary ID: KIN 2787CI101
• Status: Recruiting
• Phase: Phase 1
• Start date: August 4, 2021
• Est. completion date: December 2025

Study information

• Verified date: October 2023
• Source: Pierre Fabre Medicament
• Contact: Kinnate Clinical Operations
• Phone: 858.252.2723
• Email: clinicaltrials[@]kinnate.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: December 2025
• Est. primary completion date: December 7, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Melanoma
• Non-small Cell Lung Cancer
• Solid Tumor, Adult

Intervention

Drug:
• KIN-2787
KIN-2787 will be administered orally twice daily in 28-day cycles
• KIN-2787 and binimetinib
KIN-2787 and binimetinib will be administered orally twice daily in 28-day cycles

Locations

Country	Name	City	State
Australia	Linear Clinical Research	Perth	Western Australia
Australia	Melanoma Institute Australia	Wollstonecraft	New South Wales
China	Beijing University Cancer Hospital	Beijing
China	Linyi Cancer Hospital	Linyi	Shandong
China	The Shanghai Pulmonary Hospital	Shanghai
China	Union Hospital of Tongji Medical College of HUST	Wuhan	Hubei
France	Institut Bergonie	Bordeaux
France	Centre Leon Berard	Lyon
France	APHM-CHU La Timone	Marseille
France	CHU Nantes-Hotel Dieu	Nantes
France	Gustave Roussy	Villejuif
Korea, Republic of	Chungbuk National University Hospital	Cheongju-si
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Netherlands	Netherlands Cancer Institute	Amsterdam
Spain	Hospital Quiron Dexeus	Barcelona
Spain	Vall d'Hebron Institute of Oncology (VHIO)	Barcelona
Spain	Hospital Universitario Insular de Gran Canaria	Las Palmas De Gran Canaria
Spain	Hospital General Gregorio Marañón	Madrid
Spain	INCLIVA (Hospital Clinico de Valencia)	Valencia
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
United States	Center for Cancer and Blood Disorders	Bethesda	Maryland
United States	Cleveland Clinic	Cleveland	Ohio
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	City of Hope	Duarte	California
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Providence	Fullerton	California
United States	UCSD Moores Cancer Center	La Jolla	California
United States	UCLA	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	NYU Langone	New York	New York
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	Sarah Cannon Research Institute - Lake Nona	Orlando	Florida
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson	Philadelphia	Pennsylvania
United States	UC Davis	Sacramento	California
United States	Providence Medical Foundation (St. Joseph's)	Santa Rosa	California
United States	Stanford Cancer Center	Stanford	California
United States	Northwest Medical Specialties	Tacoma	Washington
United States	Moffitt Cancer Ceter	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pierre Fabre Medicament

Countries where clinical trial is conducted

United States,  Australia,  China,  France,  Korea, Republic of,  Netherlands,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	In Part B (Dose Expansion) - disease control rate (DCR).		Initiation of study drug until disease progression (up to approximately 36 months)
Primary	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)
Primary	In Part B (Dose Expansion) - duration of stable disease.		Initiation of study drug until disease progression (up to approximately 36 months)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)