KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors (FIT-001)

April 9, 2026 updated by: Kura Oncology, Inc.

Phase 1, First-in-Human, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of KO-2806 When Administered as Monotherapy and in Combination Therapy in Adult Patients With Advanced Solid Tumors

This first-in-human (FIH) dose-escalation and dose-validation/expansion study will assess KO-2806, a farnesyltransferase inhibitor (FTI), as a monotherapy and in combination, in adult patients with advanced solid tumors.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

300

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Lyon, France, 69495
        • Recruiting
        • Centre Leon Berard
      • Paris, France, 75015
      • Paris, France, 75013
      • Toulouse, France, 31059
        • Recruiting
        • Institut Universitaire Du Cancer Toulouse - Oncopole
  • Germany
      • Berlin, Germany, 10117
        • Recruiting
        • Charite - Universitätsmedizin Berlin
      • Berlin, Germany, 12203
        • Recruiting
        • Charite - Universitätsmedizin Berlin
      • Ulm, Germany, 89081
        • Recruiting
        • Universitätsklinikum Ulm
      • Würzburg, Germany, 97080
        • Recruiting
        • Universitatsklinikum Wurzburg
  • Italy
      • Bologna, Italy, 40138
      • Candiolo, Italy, 10060
        • Recruiting
        • Fondazione Piemonte per l'Oncologia - IRCCs Candiolo
        • Contact:
      • Naples, Italy, 80131
        • Recruiting
        • Istituto Nazionale Tumori IRCCS
      • Rozzano, Italy, 20089
        • Recruiting
        • Humanitas University
      • Verona, Italy, 37134
  • Spain
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Recruiting
        • Mayo Clinic Comprehensive Cancer Center
      • Tucson, Arizona, United States, 85724
        • Recruiting
        • University of Arizona
      • Tucson, Arizona, United States, 85721
        • Recruiting
        • University of Arizona
    • California
      • Los Angeles, California, United States, 90048
        • Recruiting
        • Cedars-Sinai Medical Center
        • Contact:
      • Los Angeles, California, United States, 90033
      • Los Angeles, California, United States, 90095
    • Colorado
    • Florida
      • Celebration, Florida, United States, 34747
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Mayo Clinic Comprehensive Cancer Center
      • Sarasota, Florida, United States, 34232
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa Hospitals & Clinics
        • Contact:
          • Mimi McKay
          • Phone Number: 319-353-8155
    • Massachusetts
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Health System
        • Contact:
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic Comprehensive Cancer Center
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Contact:
    • New Jersey
      • New Brunswick, New Jersey, United States, 08901
        • Recruiting
        • Rutgers Cancer Institute of New Jersey
        • Contact:
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Ohio State University
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • SCRI - Oncology Partners
        • Contact:
          • Phone Number: 844-482-4812
    • Texas
      • Dallas, Texas, United States, 75235
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Cancer Center
        • Contact:
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Recruiting
        • University of Wisconsin (Carbone Cancer Center)
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • At least 18 years of age.

  • Histologically or cytologically confirmed advanced solid tumors

    • Arm #1 (KO-2806 monotherapy): Patients who have progressed on, or are refractory to, standard of care (SOC) treatments with advanced solid tumors, specifically: HRAS-mutant and/or amplified tumors (any solid tumor type); HRAS overexpression (only for HNSCC tumors); KRAS and/or NRAS, and/or HRAS-mutant and/or amplified NSCLC or CRC; KRAS-mutant and/or amplified PDAC
    • Arm #2 (Combination): Patients who have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic RCC with predominantly clear cell subtype; non-clear cell RCC patients who are either treatment-naïve or have received any prior systemic treatment for locally advanced and metastatic RCC.
    • Arm #3 (Combination): Patients who have received at least 1 prior systemic therapy including available approved SOC treatments for KRAS G12C-mutant locally advanced or metastatic NSCLC, CRC, or PDAC.
    • Arm #4 (Combination): Patients must be cabozantinib-naïve and have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic ccRCC, but no more than 3 prior systemic anticancer therapies.
    • Arm #5 (Cabozantinib monotherapy): Patients must be cabozantinib-naïve and have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic ccRCC, but no more than 3 prior systemic anticancer therapies.
    • Arm #6 (Cabozantinib rollover to combination): Patients must be cabozantinib-naïve and have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic ccRCC, but no more than 3 prior systemic anticancer therapies.
    • Arm #7 (Combination): Patients who have received at least 1 prior systemic therapy including available approved SOC treatments for KRAS G12C-mutant locally advanced or metastatic NSCLC
  • Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
  • Karnofsky Performance Status of 70 or higher with no clinically significant deterioration over the previous 2 weeks.
  • Acceptable liver, renal, endocrine, and hematologic function.
  • Other protocol-defined inclusion criteria may apply.

Exclusion Criteria:

  • Any use of anticancer therapy within 14 days or 5 half-lives (whichever is shorter) of Cycle 1 Day 1.
  • Prior treatment with an FTI or HRAS inhibitor.
  • Major surgery, other than local procedures, within 28 days prior to Cycle 1 Day 1, without complete recovery.
  • Spinal cord compression, leptomeningeal disease, or clinically active CNS metastases.
  • Toxicity (excluding alopecia) from prior therapy that has not been completely resolved to baseline at the time of consent.
  • Active or prior documented autoimmune or inflammatory disorders within the past 5 years prior to Cycle 1 Day 1 (with exceptions).
  • Active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy.
  • Inability to swallow, impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the trial drugs.
  • Inadequate cardiac and/or vascular function, including receipt of treatment for unstable angina, myocardial infarction, and/or cerebrovascular attack within the prior 6 months, mean QTcF ≥470 ms, or Class II or greater congestive heart failure.
  • Other invasive malignancy within 2 years.
  • Other protocol-defined exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm #1: RAS-altered advanced solid tumors, monotherapy (escalation phase)

Patients with advanced solid tumors and the following:

  • HRAS-mutant and/or amplified tumors (any solid tumor type)
  • HRAS overexpression (only for HNSCC tumors)
  • KRAS and/or NRAS and/or HRAS-mutant and/or amplified for NSCLC or CRC
  • KRAS-mutant and/or amplified PDAC
Drug: Darlifarnib
Oral administration
Other Names:
  • KO-2806
Experimental: Arm #2: Advanced or metastatic RCC, combination therapy (escalation phase)
Patients who have received at least 1 prior systemic therapy with immuno-oncology (IO)-based treatment for locally advanced or metastatic RCC with predominantly clear cell subtype; non-clear cell RCC patients who are either treatment naïve or have received any prior systemic treatment for locally advanced and metastatic RCC
Drug: Cabozantinib
Oral administration
Other Names:
  • Cabometyx
Drug: Darlifarnib
Oral administration
Other Names:
  • KO-2806
Experimental: Arm #3: Advanced or metastatic NSCLC, CRC, or PDAC, combination therapy (escalation phase)
Patients with KRAS G12C-mutant locally advanced or metastatic NSCLC, CRC, or PDAC who have received at least 1 prior systemic therapy including available approved standard of care treatments
Drug: Adagrasib
Oral administration
Other Names:
  • Krazati
Drug: Darlifarnib
Oral administration
Other Names:
  • KO-2806
Experimental: Arm #4: Advanced or metastatic ccRCC, combination therapy (expansion phase)
Patients must be cabozantinib-naïve and have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic ccRCC
Drug: Cabozantinib
Oral administration
Other Names:
  • Cabometyx
Drug: Darlifarnib
Oral administration
Other Names:
  • KO-2806
Experimental: Arm #5: Advanced or metastatic ccRCC, monotherapy (expansion phase)
Patients must be cabozantinib-naïve and have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic ccRCC
Drug: Cabozantinib
Oral administration
Other Names:
  • Cabometyx
Experimental: Arm #6: Advanced or metastatic ccRCC, cabozantinib rollover to combination therapy (expansion phase)
Patients must be cabozantinib-naïve and have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic ccRCC
Drug: Cabozantinib
Oral administration
Other Names:
  • Cabometyx
Drug: Darlifarnib
Oral administration
Other Names:
  • KO-2806
Experimental: Arm #7: Advanced or metastatic NSCLC, combination therapy (expansion phase)
Patients with KRAS G12C-mutant locally advanced or metastatic NSCLC who have received at least 1 prior systemic therapy including available approved standard of care treatments
Drug: Adagrasib
Oral administration
Other Names:
  • Krazati
Drug: Darlifarnib
Oral administration
Other Names:
  • KO-2806

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of dose-limiting toxicities (DLTs)
Time Frame: DLTs will be evaluated during the first 28 days of KO-2806 treatment (dose escalation)
DLTs will be evaluated during the first 28 days of KO-2806 treatment (dose escalation)
Descriptive statistics of adverse events (AEs)
Time Frame: First dose of KO-2806 up to and including 28 days after last dose of KO-2806 (dose escalation)
NCI-CTCAE v5.0
First dose of KO-2806 up to and including 28 days after last dose of KO-2806 (dose escalation)
Incidence of dose interruptions, reductions, and discontinuations due to AE
Time Frame: First dose of KO-2806 up to last dose of KO-2806 or up to 24 months of treatment (dose escalation)
First dose of KO-2806 up to last dose of KO-2806 or up to 24 months of treatment (dose escalation)
Objective Response Rate (ORR)
Time Frame: Up to an estimated period of 24 months (dose expansion)
Assessed per RECIST v1.1
Up to an estimated period of 24 months (dose expansion)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: Up to an estimated period of 24 months (dose escalation)
Assessed per RECIST v1.1
Up to an estimated period of 24 months (dose escalation)
Disease control rate (DCR)
Time Frame: Up to an estimated period of 24 months (dose escalation and expansion)
Assessed per RECIST v1.1
Up to an estimated period of 24 months (dose escalation and expansion)
Duration of response (DoR)
Time Frame: Up to an estimated period of 24 months (dose escalation and expansion)
Assessed per RECIST v1.1
Up to an estimated period of 24 months (dose escalation and expansion)
Progression-Free Survival (PFS)
Time Frame: Up to an estimated period of 24 months (dose escalation and expansion)
Assessed per RECIST v1.1
Up to an estimated period of 24 months (dose escalation and expansion)
Incidence of dose interruptions, reductions, and discontinuations due to AE
Time Frame: First dose of KO-2806 up to last dose of KO-2806 or up to 24 months of treatment (dose expansion)
First dose of KO-2806 up to last dose of KO-2806 or up to 24 months of treatment (dose expansion)
Descriptive statistics of AEs
Time Frame: First dose of KO-2806 up to and including 28 days after last dose of KO-2806 (dose expansion)
NCI-CTCAE v5.0
First dose of KO-2806 up to and including 28 days after last dose of KO-2806 (dose expansion)
Time to response (TTR)
Time Frame: Up to an estimated period of 24 months (dose escalation and expansion)
Assessed per RECIST v1.1
Up to an estimated period of 24 months (dose escalation and expansion)
Overall Survival (OS)
Time Frame: First dose of KO-2806 until death, or up to an estimated period of 37 months (dose escalation and expansion)
For patients with no events, OS will be censored at the last known to be alive date
First dose of KO-2806 until death, or up to an estimated period of 37 months (dose escalation and expansion)
AUClast
Time Frame: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion)
Area under the curve from time zero to last measurable concentration for KO-2806 (in the absence and presence of food) and combination agent.
Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion)
AUC0-inf
Time Frame: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion)
Area under the curve from time zero to infinity post administration for KO-2806 (in the absence and presence of food) and combination agent
Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion)
Cmax
Time Frame: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion)
Maximum plasma concentration (Cmax) of KO-2806 (in the absence and presence of food) and the combination agent
Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion)
Cmin
Time Frame: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion)
Minimum plasma concentration (Cmin) of KO-2806 (in the absence and presence of food) and the combination agent
Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion)
Tmax
Time Frame: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion)
Time to maximal concentration (Tmax) of KO-2806 (in the absence and presence of food) and the combination agent
Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion)
Estimated terminal elimination rate constant (λz)
Time Frame: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion)
Estimated terminal elimination rate constant of KO-2806 and the combination agent
Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion)
t1/2
Time Frame: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion)
Half-life (t1/2) of KO-2806 (in the absence and presence of food) and the combination agent
Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion)
CL/F
Time Frame: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion)
Total apparent clearance (CL/F) of KO-2806 and the combination agent
Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion)
Vd/F
Time Frame: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion)
Total apparent volume of distribution (Vd/F) of KO-2806 and the combination agent
Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion)
QTcF
Time Frame: Up to 28 days following last dose of KO-2806, cabozantinib, or adagrasib. (Dose escalation and dose expansion)
QT interval corrected for heart rate (HR) using Fridericia's formula (QTcF) for KO-2806 monotherapy and in combination
Up to 28 days following last dose of KO-2806, cabozantinib, or adagrasib. (Dose escalation and dose expansion)
KO-2806 plasma concentration measurements
Time Frame: Up to day 28 following first dose of KO-2806 and adagrasib. (Dose escalation and dose expansion)
Up to day 28 following first dose of KO-2806 and adagrasib. (Dose escalation and dose expansion)
Amount of KO-2806 excretion in urine
Time Frame: Up to 24 hours following first dose of KO-2806. (Dose escalation)
Up to 24 hours following first dose of KO-2806. (Dose escalation)
CLr of KO-2806 excretion in urine
Time Frame: Up to 24 hours following first dose of KO-2806. (Dose escalation)
Renal clearance of KO-2806 excretion in urine
Up to 24 hours following first dose of KO-2806. (Dose escalation)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kura Oncology, Inc.

Collaborators

Mirati Therapeutics Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 18, 2023

Primary Completion (Estimated)

January 1, 2027

Study Completion (Estimated)

April 1, 2027

Study Registration Dates

First Submitted

August 17, 2023

First Submitted That Met QC Criteria

August 30, 2023

First Posted (Actual)

September 7, 2023

Study Record Updates

Last Update Posted (Actual)

April 14, 2026

Last Update Submitted That Met QC Criteria

April 9, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KO-2806-001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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