KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors

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

  • Solid Tumors With HRAS Alterations
  • Non Small Cell Lung Cancer (NSCLC)
  • Colorectal Cancer (CRC)
  • Pancreatic Ductal Adenocarcinoma (PDAC)
  • Clear Cell Renal Cell Carcinoma (ccRCC)
  • Renal Cell Carcinoma (Kidney Cancer)

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