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

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ClinicalTrials.gov Identifier: NCT04913285
Recruitment Status : Recruiting
First Posted : June 4, 2021
Last Update Posted : September 1, 2022
Sponsor:
Information provided by (Responsible Party):
Kinnate Biopharma

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.

Condition or disease Intervention/treatment Phase
Solid Tumor, Adult Non-small Cell Lung Cancer Melanoma Drug: KIN-2787 Drug: KIN-2787 and binimetinib Phase 1

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 II or III mutations, including lung cancer, melanoma, and other selected solid tumors.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 155 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Actual Study Start Date : August 4, 2021
Estimated Primary Completion Date : March 2024
Estimated Study Completion Date : June 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Binimetinib

Arm Intervention/treatment
Experimental: Dose Escalation Monotherapy (Part A1)
Dose escalation of KIN-2787
Drug: KIN-2787
KIN-2787 will be administered orally twice daily in 28-day cycles

Experimental: Dose Escalation Combination therapy (Part A2)
Dose escalation of KIN-2787 and binimetinib
Drug: KIN-2787 and binimetinib
KIN-2787 and binimetinib will be administered orally twice daily in 28-day cycles

Experimental: Dose Expansion (Part B)
Dose expansion evaluating the recommended phase 2 dose (RP2D) of KIN-2787
Drug: KIN-2787
KIN-2787 will be administered orally twice daily in 28-day cycles




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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

  4. In Part B (Dose Expansion) - disease control rate (DCR). [ Time Frame: Initiation of study drug until disease progression (up to approximately 36 months) ]
  5. 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

  6. In Part B (Dose Expansion) - duration of stable disease. [ Time Frame: Initiation of study drug until disease progression (up to approximately 36 months) ]

Secondary Outcome Measures :
  1. 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) ]
  2. 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) ]
  3. 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) ]
  4. 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) ]
  5. 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) ]
  6. 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) ]
  7. Part B Dose Expansion: characterization of PK properties 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) ]
  8. Part B Dose Expansion: characterization of PK properties 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) ]
  9. Part B Dose Expansion: characterization of PK properties 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) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 or evaluable disease by RECIST v1.1.
  • ECOG performance status 0, 1, or 2.
  • Adequate organ function, as measured by laboratory values (criteria listed in protocol).
  • Able to swallow, retain, and absorb oral medications.

Exclusion Criteria:

  • Known clinically-active or clinically-progressive brain metastases from non-brain tumors.
  • 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.
  • In Part B Dose Expansion, patients with BRAF Class I mutations are excluded.

Complete inclusion and exclusion criteria are listed in the clinical study protocol.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04913285


Contacts
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Contact: Kinnate Clinical Operations clinicaltrials@kinnate.com

Locations
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Sponsors and Collaborators
Kinnate Biopharma
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Responsible Party: Kinnate Biopharma
ClinicalTrials.gov Identifier: NCT04913285    
Other Study ID Numbers: KN-8701
First Posted: June 4, 2021    Key Record Dates
Last Update Posted: September 1, 2022
Last Verified: August 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kinnate Biopharma:
BRAF inhibitor
BRAF
pan-RAF
pan-RAF inhibitor
RAF1
ARAF
BRAF alteration
BRAF Class II
BRAF Class III
V600
tumor growth inhibitor (TGI)
melanoma
NSCLC
solid tumor
targeted therapy
BRAF Class I
NRAS
Metastatic
Unresectable
CRC
ATC
Colon
Thyroid
Advanced
Additional relevant MeSH terms:
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Melanoma
Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas