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

• ClinicalTrials.gov Identifier: NCT04913285
• Recruitment Status: Recruiting
• First Posted: June 4, 2021
• Last Update Posted: March 12, 2024
• Sponsor: Kinnate Biopharma
• Information provided by (Responsible Party): Kinnate Biopharma

Tracking Information

• First Submitted Date: May 18, 2021
• First Posted Date: June 4, 2021
• Last Update Posted Date: March 12, 2024
• Actual Study Start Date: August 4, 2021
• Estimated Primary Completion Date: March 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 6, 2023)

• Part A1 Dose escalation monotherapy: [ Time Frame: 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 [ Time Frame: 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. [ Time Frame: 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
• In Part B (Dose Expansion) - disease control rate (DCR). [ Time Frame: Initiation of study drug until disease progression (up to approximately 36 months) ]
• In Part B (Dose Expansion) - duration of overall response (DOR). [ Time Frame: 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) - duration of stable disease. [ Time Frame: Initiation of study drug until disease progression (up to approximately 36 months) ]

Original Primary Outcome Measures (submitted: May 28, 2021)

• Incidence of dose limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), and incidence of clinically significant changes in vital signs, physical examinations, ECGs, and clinical laboratory tests. [ Time Frame: 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. [ Time Frame: Initiation of study drug until disease progression (up to approximately 36 months) ]
• In Part B (dose expansion) - disease control rate (DCR). [ Time Frame: Initiation of study drug until disease progression (up to approximately 36 months) ]
• In Part B (dose expansion) - duration of overall response (DOR). [ Time Frame: 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) - duration of stable disease. [ Time Frame: Initiation of study drug until disease progression (up to approximately 36 months) ]

Current Secondary Outcome Measures (submitted: October 6, 2023)

• Part A1 Dose Escalation: Characterization of PK properties and effect of food on PK of KIN-2787 including, but not limited to tmax. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months) ]

Original Secondary Outcome Measures (submitted: May 28, 2021)

• Maximum observed plasma concentration (Cmax) of KIN-2787 [ Time Frame: Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months) ]
• Time to achieve Cmax (Tmax) [ Time Frame: Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months) ]
• Area under the plasma concentration-time curve (AUC). [ Time Frame: Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate KIN-2787 in Participants With BRAF and/or NRAS Mutation Positive Solid Tumors
• 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.
• 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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

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

Study Arms

• Experimental: Dose Escalation Monotherapy (Part A1)
  Dose escalation of KIN-2787
  Intervention: Drug: KIN-2787
• Experimental: Dose Escalation Combination therapy (Part A2)
  Dose escalation of KIN-2787 and binimetinib
  Intervention: Drug: KIN-2787 and binimetinib
• Experimental: Dose Expansion Monotherapy (Part B1)
  Dose expansion evaluating the recommended phase 2 dose (RP2D) of KIN-2787
  Intervention: Drug: KIN-2787
• Experimental: Dose Escalation Combination therapy (Part B2)
  Dose expansion evaluating the recommended phase 2 dose (RP2D) of KIN-2787 and binimetinib
  Intervention: Drug: KIN-2787 and binimetinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 6, 2023): 400
• Original Estimated Enrollment (submitted: May 28, 2021): 115
• Estimated Study Completion Date: June 2024
• Estimated Primary Completion Date: March 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Kinnate Clinical Operations; 858.252.2723; clinicaltrials@kinnate.com

• Listed Location Countries: Australia, China, France, Korea, Republic of, Netherlands, Spain, Taiwan, United States

Administrative Information

• NCT Number: NCT04913285
• Other Study ID Numbers: KN-8701
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Kinnate Biopharma
• Original Responsible Party: Same as current
• Current Study Sponsor: Kinnate Biopharma
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Kinnate Biopharma
• Verification Date: October 2023