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Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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): 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 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. - 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.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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: Darlifarnib
    Oral administration
    Other names:
    • KO-2806
Experimental
Arm #2: Advanced or metastatic RCC 		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
  • Drug: Darlifarnib
    Oral administration
    Other names:
    • KO-2806
  • Drug: Cabozantinib
    Oral administration
    Other names:
    • Cabometyx
Experimental
Arm #3: Advanced or metastatic NSCLC, CRC, or PDAC 		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: Darlifarnib
    Oral administration
    Other names:
    • KO-2806
  • Drug: Adagrasib
    Oral administration
    Other names:
    • Krazati

Recruiting Locations

Washington University in St. Louis and nearby locations

Washington University School of Medicine
St Louis 4407066, Missouri 4398678 63110
Contact:
Jessica Ley
314-747-8092
jcley@wustl.edu

More Details

NCT ID
NCT06026410
Status
Recruiting
Sponsor
Kura Oncology, Inc.

Study Contact

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

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.