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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT06026410
Recruitment Status : Recruiting
First Posted : September 7, 2023
Last Update Posted : April 8, 2024
Sponsor:
Collaborator:
Mirati Therapeutics Inc.
Information provided by (Responsible Party):
Kura Oncology, Inc.

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

Condition or disease Intervention/treatment Phase
Solid Tumors With HRAS Alterations Non Small Cell Lung Cancer (NSCLC) Colorectal Cancer (CRC) Pancreatic Ductal Adenocarcinoma (PDAC) Clear Cell Renal Cell Carcinoma (ccRCC) Drug: KO-2806 Drug: Cabozantinib Drug: Adagrasib Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 270 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 18, 2023
Estimated Primary Completion Date : January 2027
Estimated Study Completion Date : April 2027

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm #1: RAS-altered advanced solid tumors

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: KO-2806
Oral administration
Experimental: Arm #2: Advanced or metastatic ccRCC
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
 Drug: KO-2806
Oral administration

Drug: Cabozantinib
Oral administration
Other Name: Cabometyx
Experimental: Arm #3: Advanced or metastatic NSCLC
Patients with KRAS G12C-mutant locally advanced or metastatic NSCLC who have received at least 1 prior systemic therapy for advanced or metastatic NSCLC
 Drug: KO-2806
Oral administration

Drug: Adagrasib
Oral administration
Other Name: Krazati


Outcome Measures
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Primary Outcome Measures :
  1. Rate of dose-limiting toxicities (DLTs) [ Time Frame: DLTs will be evaluated during the first 28 days of KO-2806 treatment (dose escalation) ]
  2. Descriptive statistics of adverse events [ Time Frame: First dose of KO-2806 up to and including 28 days after last dose of KO-2806, or if the patient is lost to follow-up, whichever comes first (dose escalation) ]
    NCI-CTCAE v5.0

  3. Overall Response Rate (ORR) [ Time Frame: Up to an estimated period of 24 months (dose expansion) ]
    Assessed per RECIST v1.1


Secondary Outcome Measures :
  1. Rate of dose-limiting toxicities (DLTs) [ Time Frame: DLTs will be evaluated during the first 28 days of KO-2806 treatment (dose expansion) ]
  2. Descriptive statistics of adverse events [ Time Frame: First dose of KO-2806 up to and including 28 days after last dose of KO-2806, or if the patient is lost to follow-up, whichever comes first (dose expansion) ]
    NCI-CTCAE v5.0

  3. Objective Response Rate (ORR) [ Time Frame: Up to an estimated period of 24 months (dose escalation) ]
    Assessed per RECIST v1.1

  4. Disease control rate (DCR) [ Time Frame: Up to an estimated period of 24 months (dose escalation and expansion) ]
    Assessed per RECIST v1.1

  5. Duration of response (DoR) [ Time Frame: Up to an estimated period of 24 months (dose escalation and expansion) ]
    Assessed per RECIST v1.1

  6. Progression-Free Survival (PFS) [ Time Frame: Up to an estimated period of 24 months (dose escalation and expansion) ]
    Assessed per RECIST v1.1

  7. Overall Survival (OS) [ Time Frame: Up to an estimated period of 24 months (dose escalation and expansion) ]
    Assessed per RECIST v1.1

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. QTcF [ Time Frame: Up to day 7 following first dose of KO-2806 and adagrasib. Dose escalation. ]
    QT interval corrected for heart rate (HR) using Fridericia's formula (QTcF) for KO-2806 monotherapy and in combination

  18. KO-2806 plasma concentration measurements [ Time Frame: Up to day 28 following first dose of KO-2806 and adagrasib. Dose escalation. ]
  19. Amount of KO-2806 excretion in urine [ Time Frame: Up to 24 hours following first dose of KO-2806. Dose escalation. ]
  20. 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


Eligibility Criteria
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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:

  • At least 18 years of age.

  • Histologically or cytologically confirmed advanced solid tumors

    • Arm #1 (Monotherapy): 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): Must have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic RCC with predominantly clear cell subtype
    • Arm #3 (Combination): Must have KRAS G12C-mutant locally advanced or metastatic NSCLC and have received at least 1 prior systemic therapy for 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:

  • Ongoing treatment with certain anticancer agents.
  • 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 cerebro-vascular 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.
Contacts and Locations
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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): NCT06026410


Contacts
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Contact: Clinical Operations 617-588-3755 KO-2806-001@kuraoncology.com

Locations
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United States, California
University of Southern California Recruiting
Los Angeles, California, United States, 90033
Contact: Xiomara Menendez, RN    323-865-3000    Xiomara.Menendez@med.usc.edu   
UCLA Department of Medicine Recruiting
Los Angeles, California, United States, 90095
Contact: Christopher Lim    310-633-8400 ext 16043    christopherlim@mednet.ucla.edu   
United States, Colorado
Sarah Cannon Research Institute at HealthONE Recruiting
Denver, Colorado, United States, 80218
Contact    720-754-2610    CANN.DDUDenverGeneral@sarahcannon.com   
United States, Florida
AdventHealth Celebration Recruiting
Celebration, Florida, United States, 34747
Contact: Amy Whitaker       amy.whitaker@adventhealth.com   
Florida Cancer Specialists Recruiting
Sarasota, Florida, United States, 34232
Contact: Nancy Olsen       nolsen@flcancer.com   
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Emily McClure, RN    857-215-0180    Emily_mcclure@dfci.harvard.edu   
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Jessica Ley    314-747-8092    jcley@wustl.edu   
United States, Oklahoma
OU Stephenson Cancer Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Christina Caldwell    405-271-8001 ext 48171    Christina-Caldwell@ouhsc.edu   
United States, Tennessee
SCRI - Oncology Partners Recruiting
Nashville, Tennessee, United States, 37203
Contact    844-482-4812      
United States, Wisconsin
University of Wisconsin (Carbone Cancer Center) Recruiting
Madison, Wisconsin, United States, 53792
Contact: UW Carbone Cancer Center - Cancer Connect    800-622-8922    cancerconnect@uwcarbone.wisc.edu   
Sponsors and Collaborators
Kura Oncology, Inc.
Mirati Therapeutics Inc.
More Information
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Responsible Party: Kura Oncology, Inc.
ClinicalTrials.gov Identifier: NCT06026410    
Other Study ID Numbers: KO-2806-001
First Posted: September 7, 2023    Key Record Dates
Last Update Posted: April 8, 2024
Last Verified: April 2024

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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 Kura Oncology, Inc.:
HRAS
KRAS
NRAS
Farnesyl transferase inhibitor (FTI)
Tyrosine Kinase inhibitor (TKI)
 Phase 1
KRAS G12C inhibitor
NSCLC
ccRCC
Additional relevant MeSH terms:
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Carcinoma, Renal Cell
Neoplasms
Neoplasms by Site
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Neoplasms
Urologic Neoplasms
 Urogenital Neoplasms
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Kidney Diseases
Urologic Diseases
Male Urogenital Diseases
Adagrasib
Antineoplastic Agents