KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors

NCT06026410
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Phase
Phase 1
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Recruitment status
Recruiting
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Participants
300
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Lead sponsor
Kura Oncology, Inc.
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Start date
2023-10-18
clinicaltrials.gov
Number of sites
38
clinicaltrials.gov

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.
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Acronym
FIT-001
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Short title
KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors
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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
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1
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Study type
Interventional
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Completion date
2027-04-01
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First posted
2023-09-07
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Registry last updated
2026-06-08
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Primary completion date
2027-01-01
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Start date
2023-10-18
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Participants
300
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Participant count basis
Estimated
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Planned participants
300
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Protocol amendments
7
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Number of sites
38
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
Kura Oncology, Inc.
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06026410
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ClinicalTrials.gov ID
NCT06026410
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Registry record
Open registry record
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Allocation
Not randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Rate of dose-limiting toxicities (DLTs)

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

  2. Descriptive statistics of adverse events (AEs)

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

    NCI-CTCAE v5.0

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

    Timeframe: 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)

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

    Assessed per RECIST v1.1

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

    Timeframe: 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

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

    NCI-CTCAE v5.0

  3. Objective Response Rate (ORR)

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

    Assessed per RECIST v1.1

  4. Disease control rate (DCR)

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

    Assessed per RECIST v1.1

  5. Duration of response (DoR)

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

    Assessed per RECIST v1.1

  6. Time to response (TTR)

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

    Assessed per RECIST v1.1

  7. Progression-Free Survival (PFS)

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

    Assessed per RECIST v1.1

  8. Overall Survival (OS)

    Timeframe: 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

  9. AUClast

    Timeframe: 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.

  10. AUC0-inf

    Timeframe: 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

  11. Cmax

    Timeframe: 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

  12. Cmin

    Timeframe: 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

  13. Tmax

    Timeframe: 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

  14. Estimated terminal elimination rate constant (λz)

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

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

  15. t1/2

    Timeframe: 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

  16. CL/F

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

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

  17. Vd/F

    Timeframe: 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

  18. QTcF

    Timeframe: 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

  19. KO-2806 plasma concentration measurements

    Timeframe: 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

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

  21. CLr of KO-2806 excretion in urine

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

    Renal clearance of KO-2806 excretion in urine

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • 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.

  • 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.
Sources for eligibility
clinicaltrials.gov

  • Mayo Clinic Comprehensive Cancer CenterPhoenix, United StatesRecruiting
  • University of ArizonaTucson, United StatesRecruiting
  • University of Southern CaliforniaLos Angeles, United StatesRecruiting
  • Cedars-Sinai Medical CenterLos Angeles, United StatesRecruiting
  • UCLA Department of MedicineLos Angeles, United StatesRecruiting
  • Sarah Cannon Research Institute at HealthONEDenver, United StatesRecruiting
  • AdventHealth CelebrationCelebration, United StatesRecruiting
  • Mayo Clinic Comprehensive Cancer CenterJacksonville, United StatesRecruiting
  • Florida Cancer SpecialistsSarasota, United StatesRecruiting
  • University of Iowa Hospitals & ClinicsIowa City, United StatesRecruiting
  • Dana-Farber Cancer InstituteBoston, United StatesRecruiting
  • Henry Ford Health SystemDetroit, United StatesRecruiting
  • Mayo Clinic Comprehensive Cancer CenterRochester, United StatesRecruiting
  • Washington University School of MedicineSt Louis, United StatesRecruiting
  • Rutgers Cancer Institute of New JerseyNew Brunswick, United StatesRecruiting
  • Ohio State UniversityColumbus, United StatesRecruiting
  • OU Stephenson Cancer CenterOklahoma City, United StatesRecruiting
  • UPMC Hillman Cancer CenterPittsburgh, United StatesRecruiting
  • SCRI - Oncology PartnersNashville, United StatesRecruiting
  • UT Southwestern Simmons Cancer CenterDallas, United StatesRecruiting
  • MD Anderson Cancer CenterHouston, United StatesRecruiting
  • University of Wisconsin (Carbone Cancer Center)Madison, United StatesRecruiting
  • Centre Leon BerardLyon, FranceRecruiting
  • Oncologie médicale - Pitié-SalpêtrièreParis, FranceRecruiting
  • Hopital Européen Georges PompidouParis, FranceRecruiting

And 13 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

Related records

Drugs (2)

Collaborators (1)

Lead sponsors (1)

Conditions (7)

Targets (3)