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Solid Tumors With HRAS AlterationsPhase 1FIT-001NCT06026410

KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors

A Phase 1 study testing Darlifarnib, Cabozantinib and Adagrasib in people with Solid Tumors With HRAS Alterations and Non Small Cell Lung Cancer (NSCLC), run by Kura Oncology, Inc. at 38 sites in 5 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record

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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Darlifarnib, Cabozantinib and Adagrasib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
300 participants
Where
38 sitesin 5 countries
Study dates
18 Oct 2023to Apr 2027
Phase
Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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).
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  • 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.

Trial locations and contacts

38 sites in 5 countries. Contact the study team or a site near you to ask about taking part.

Kura Medical Information contact

844-KURAONC (844-587-2662)

medinfo@kuraoncology.com

38 sites in 5 countries

United States22 sites, 22 recruiting

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

    Recruiting

  • AdventHealth Celebration

    Celebration, Florida, 34747

    Recruiting

  • Ohio State University

    Columbus, Ohio, 43210

    Recruiting

  • UT Southwestern Simmons Cancer Center

    Dallas, Texas, 75235

    Recruiting

  • Sarah Cannon Research Institute at HealthONE

    Denver, Colorado, 80218

    Recruiting

  • Henry Ford Health System

    Detroit, Michigan, 48202

    Recruiting

  • MD Anderson Cancer Center

    Houston, Texas, 77030

    Recruiting

  • University of Iowa Hospitals & Clinics

    Iowa City, Iowa, 52242

    Recruiting

  • Mayo Clinic Comprehensive Cancer Center

    Jacksonville, Florida, 32224

    Recruiting

  • University of Southern California

    Los Angeles, California, 90033

    Recruiting

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

    Recruiting

  • UCLA Department of Medicine

    Los Angeles, California, 90095

    Recruiting

  • University of Wisconsin (Carbone Cancer Center)

    Madison, Wisconsin, 53792

    Recruiting

  • SCRI - Oncology Partners

    Nashville, Tennessee, 37203

    Recruiting

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08901

    Recruiting

  • OU Stephenson Cancer Center

    Oklahoma City, Oklahoma, 73104

    Recruiting

  • Mayo Clinic Comprehensive Cancer Center

    Phoenix, Arizona, 85054

    Recruiting

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

    Recruiting

  • Mayo Clinic Comprehensive Cancer Center

    Rochester, Minnesota, 55905

    Recruiting

  • Florida Cancer Specialists

    Sarasota, Florida, 34232

    Recruiting

  • Washington University School of Medicine

    St Louis, Missouri, 63110

    Recruiting

  • University of Arizona

    Tucson, Arizona, 85724

    Recruiting

Other trials in United States

Italy5 sites, 5 recruiting

  • Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS

    Bologna, 40138

    Recruiting

  • Fondazione Piemonte per l'Oncologia - IRCCs Candiolo

    Candiolo, 10060

    Recruiting

  • Istituto Nazionale Tumori IRCCS

    Naples, 80131

    Recruiting

  • Humanitas University

    Rozzano, 20089

    Recruiting

  • AOU Verona - Centro Ricerche Cliniche di Verona

    Verona, 37134

    Recruiting

Other trials in Italy

France4 sites, 4 recruiting

  • Centre Leon Berard

    Lyon, 69495

    Recruiting

  • Oncologie médicale - Pitié-Salpêtrière

    Paris, 75013

    Recruiting

  • Hopital Européen Georges Pompidou

    Paris, 75015

    Recruiting

  • Institut Universitaire du Cancer Toulouse - Oncopole

    Toulouse, 31059

    Recruiting

Other trials in France

Spain4 sites, 4 recruiting

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

    Recruiting

  • Hospital de la Santa Creu i de Sant Pau

    Barcelona, 08041

    Recruiting

  • Hospital HM Sanchinarro START Madrid-CIOCC

    Madrid, 28050

    Recruiting

  • Hospital Universitario Virgen del Rocío

    Seville, 41013

    Recruiting

Other trials in Spain

Germany3 sites, 3 recruiting

  • Charité - Universitätsmedizin Berlin

    Berlin, 12203

    Recruiting

  • Universitätsklinikum Ulm

    Ulm, 89081

    Recruiting

  • Universitätsklinikum Würzburg

    Würzburg, 97080

    Recruiting

Other trials in Germany

About this study

Official title: 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.

Being tested
Darlifarnib, Cabozantinib, Adagrasib
Keywords
HRAS, KRAS, NRAS, Farnesyltransferase inhibitor (FTI), Tyrosine Kinase inhibitor (TKI), Phase 1, KRAS G12C inhibitor, NSCLC, ccRCC, RCC, PDAC, CRC
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Carcinoma, Renal Cell, Kidney Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DarlifarnibDrug

    Also called KO-2806

    Oral administration

  • CabozantinibDrug

    Also called Cabometyx

    Oral administration

  • AdagrasibDrug

    Also called Krazati

    Oral administration

Study groups in NCT06026410
Study groupRoleWhat they receive
Arm #1: RAS-altered advanced solid tumors, monotherapy (escalation phase)ExperimentalPatients 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
Receives: Drug: Darlifarnib
Arm #2: Advanced or metastatic RCC, combination therapy (escalation phase)ExperimentalPatients 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
Receives: Drug: Darlifarnib; Drug: Cabozantinib
Arm #3: Advanced or metastatic NSCLC, CRC, or PDAC, combination therapy (escalation phase)ExperimentalPatients 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
Receives: Drug: Darlifarnib; Drug: Adagrasib
Arm #4: Advanced or metastatic ccRCC, combination therapy (expansion phase)ExperimentalPatients must be cabozantinib-naïve and have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic ccRCC
Receives: Drug: Darlifarnib; Drug: Cabozantinib
Arm #5: Advanced or metastatic ccRCC, monotherapy (expansion phase)ExperimentalPatients must be cabozantinib-naïve and have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic ccRCC
Receives: Drug: Cabozantinib
Arm #6: Advanced or metastatic ccRCC, cabozantinib rollover to combination therapy (expansion phase)ExperimentalPatients must be cabozantinib-naïve and have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic ccRCC
Receives: Drug: Darlifarnib; Drug: Cabozantinib
Arm #7: Advanced or metastatic NSCLC, combination therapy (expansion phase)ExperimentalPatients 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
Receives: Drug: Darlifarnib; Drug: Adagrasib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of dose-limiting toxicities (DLTs)

    Measured: DLTs will be evaluated during the first 28 days of KO-2806 treatment (dose escalation)

  2. Descriptive statistics of adverse events (AEs)

    NCI-CTCAE v5.0

    Measured: First dose of KO-2806 up to and including 28 days after last dose of KO-2806 (dose escalation)

  3. Incidence of dose interruptions, reductions, and discontinuations due to AE

    Measured: First dose of KO-2806 up to last dose of KO-2806 or up to 24 months of treatment (dose escalation)

  4. Objective Response Rate (ORR)

    Assessed per RECIST v1.1

    Measured: Up to an estimated period of 24 months (dose expansion)

Secondary outcomes (21)

  1. Incidence of dose interruptions, reductions, and discontinuations due to AE

    Measured: First dose of KO-2806 up to last dose of KO-2806 or up to 24 months of treatment (dose expansion)

  2. Descriptive statistics of AEs

    NCI-CTCAE v5.0

    Measured: First dose of KO-2806 up to and including 28 days after last dose of KO-2806 (dose expansion)

  3. Objective Response Rate (ORR)

    Assessed per RECIST v1.1

    Measured: Up to an estimated period of 24 months (dose escalation)

  4. Disease control rate (DCR)

    Assessed per RECIST v1.1

    Measured: Up to an estimated period of 24 months (dose escalation and expansion)

  5. Duration of response (DoR)

    Assessed per RECIST v1.1

    Measured: Up to an estimated period of 24 months (dose escalation and expansion)

  6. Time to response (TTR)

    Assessed per RECIST v1.1

    Measured: Up to an estimated period of 24 months (dose escalation and expansion)

  7. Progression-Free Survival (PFS)

    Assessed per RECIST v1.1

    Measured: Up to an estimated period of 24 months (dose escalation and expansion)

  8. Overall Survival (OS)

    For patients with no events, OS will be censored at the last known to be alive date

    Measured: First dose of KO-2806 until death, or up to an estimated period of 37 months (dose escalation and expansion)

  9. AUClast

    Area under the curve from time zero to last measurable concentration for KO-2806 (in the absence and presence of food) and combination agent.

    Measured: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion)

  10. AUC0-inf

    Area under the curve from time zero to infinity post administration for KO-2806 (in the absence and presence of food) and combination agent

    Measured: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion)

  11. Cmax

    Maximum plasma concentration (Cmax) of KO-2806 (in the absence and presence of food) and the combination agent

    Measured: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion)

  12. Cmin

    Minimum plasma concentration (Cmin) of KO-2806 (in the absence and presence of food) and the combination agent

    Measured: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion)

  13. Tmax

    Time to maximal concentration (Tmax) of KO-2806 (in the absence and presence of food) and the combination agent

    Measured: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion)

  14. Estimated terminal elimination rate constant (λz)

    Estimated terminal elimination rate constant of KO-2806 and the combination agent

    Measured: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion)

  15. t1/2

    Half-life (t1/2) of KO-2806 (in the absence and presence of food) and the combination agent

    Measured: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion)

  16. CL/F

    Total apparent clearance (CL/F) of KO-2806 and the combination agent

    Measured: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion)

  17. Vd/F

    Total apparent volume of distribution (Vd/F) of KO-2806 and the combination agent

    Measured: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion)

  18. QTcF

    QT interval corrected for heart rate (HR) using Fridericia's formula (QTcF) for KO-2806 monotherapy and in combination

    Measured: Up to 28 days following last dose of KO-2806, cabozantinib, or adagrasib. (Dose escalation and dose expansion)

  19. KO-2806 plasma concentration measurements

    Measured: Up to day 28 following first dose of KO-2806 and adagrasib. (Dose escalation and dose expansion)

  20. Amount of KO-2806 excretion in urine

    Measured: Up to 24 hours following first dose of KO-2806. (Dose escalation)

  21. CLr of KO-2806 excretion in urine

    Renal clearance of KO-2806 excretion in urine

    Measured: Up to 24 hours following first dose of KO-2806. (Dose escalation)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Sep 2023
  2. Study start18 Oct 2023
  3. Primary completionJan 2027 (estimated)
  4. Study completionApr 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
300 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06026410
Sponsor's protocol ID
KO-2806-001
Acronym
FIT-001
Status last verified
Jun 2026
First submitted
17 Aug 2023
Last updated
14 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

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