Recruiting
Phase 1

KO-2806

Sponsor:

Kura Oncology, Inc.

Code:

NCT06026410

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)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Darlifarnib

Cabozantinib

Adagrasib

Study Details

Brief 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.

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)

Study ID

NCT06026410

Start date

Oct 18, 2023

Status verified date

Jun, 2026

Completion date

Apr, 2027

Anticipated

Primary completion date

Jan, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Design

Enrollment

300 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm #1: RAS-altered advanced solid tumors, monotherapy (escalation phase)

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

experimental: Arm #2: Advanced or metastatic RCC, combination therapy (escalation phase)

Patients 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

experimental: Arm #3: Advanced or metastatic NSCLC, CRC, or PDAC, combination therapy (escalation phase)

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

experimental: Arm #4: Advanced or metastatic ccRCC, combination therapy (expansion phase)

Patients must be cabozantinib-naïve and have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic ccRCC

experimental: Arm #5: Advanced or metastatic ccRCC, monotherapy (expansion phase)

Patients must be cabozantinib-naïve and have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic ccRCC

experimental: Arm #6: Advanced or metastatic ccRCC, cabozantinib rollover to combination therapy (expansion phase)

Patients must be cabozantinib-naïve and have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic ccRCC

experimental: Arm #7: Advanced or metastatic NSCLC, combination therapy (expansion phase)

Patients 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

Interventions

Darlifarnib

Oral administration

Cabozantinib

Oral administration

Adagrasib

Oral administration

Primary outcome measure

  • Rate of dose-limiting toxicities (DLTs) [ Time Frame: DLTs will be evaluated during the first 28 days of KO-2806 treatment (dose escalation) ]
  • Descriptive statistics of adverse events (AEs) [ Time Frame: First dose of KO-2806 up to and including 28 days after last dose of KO-2806 (dose escalation) ]
  • Incidence of dose interruptions, reductions, and discontinuations due to AE [ Time Frame: First dose of KO-2806 up to last dose of KO-2806 or up to 24 months of treatment (dose escalation) ]
  • Objective Response Rate (ORR) [ Time Frame: Up to an estimated period of 24 months (dose expansion) ]

Central Contacts and Locations

Central contacts

Kura Medical Information

844-KURAONC (844-587-2662)medinfo@kuraoncology.com

Locations

Mayo Clinic Comprehensive Cancer Center

Recruiting

Phoenix, Arizona, United States, 85054

University of Arizona

Recruiting

Tucson, Arizona, United States, 85724

University of Southern California

Recruiting

Los Angeles, California, United States, 90033

Contacts

Xiomara Menendez, RN

323-865-3000Xiomara.Menendez@med.usc.edu

Cedars-Sinai Medical Center

Recruiting

Los Angeles, California, United States, 90048

Contacts

William Mills

310-423-0102william.mills@cshs.org

UCLA Department of Medicine

Recruiting

Los Angeles, California, United States, 90095

Contacts

Christopher Lim

310-633-8400christopherlim@mednet.ucla.edu

Sarah Cannon Research Institute at HealthONE

Recruiting

Denver, Colorado, United States, 80218

Contacts

720-754-2610CANN.DDUDenverGeneral@sarahcannon.com

AdventHealth Celebration

Recruiting

Celebration, Florida, United States, 34747

Contacts

Amy Whitaker

amy.whitaker@adventhealth.com

Mayo Clinic Comprehensive Cancer Center

Recruiting

Jacksonville, Florida, United States, 32224

Florida Cancer Specialists

Recruiting

Sarasota, Florida, United States, 34232

Contacts

Nancy Olsen

nolsen@flcancer.com

University of Iowa Hospitals & Clinics

Recruiting

Iowa City, Iowa, United States, 52242

Contacts

Mimi McKay

319-353-8155

Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Kailene Sullivan, RN

kailene_sullivan@dfci.harvard.edu

Henry Ford Health System

Recruiting

Detroit, Michigan, United States, 48202

Contacts

Bethany Adams, RN

248-224-7345badams19@HFHS.ORG

Mayo Clinic Comprehensive Cancer Center

Recruiting

Rochester, Minnesota, United States, 55905

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Jessica Ley

314-747-8092jcley@wustl.edu

Rutgers Cancer Institute of New Jersey

Recruiting

New Brunswick, New Jersey, United States, 08901

Contacts

Mohammad Ghalib

718-405-8515mhg68@cinj.rutgers.edu

Ohio State University

Recruiting

Columbus, Ohio, United States, 43210

OU Stephenson Cancer Center

Recruiting

Oklahoma City, Oklahoma, United States, 73104

Contacts

Christina Caldwell

405-271-8001Christina-Caldwell@ouhsc.edu

UPMC Hillman Cancer Center

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Contacts

Immunotherapy and Drug Development Center (IDDC) Referrals

ClinicalResearchServicesHCCIDDC@upmc.edu

SCRI - Oncology Partners

Recruiting

Nashville, Tennessee, United States, 37203

Contacts

844-482-4812

UT Southwestern Simmons Cancer Center

Recruiting

Dallas, Texas, United States, 75235

Contacts

Tian Zhang, MD

Tian.Zhang@utsouthwestern.edu

MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Ly M Nguyen

(832) 794-3672lmnguyen1@mdanderson.org

University of Wisconsin (Carbone Cancer Center)

Recruiting

Madison, Wisconsin, United States, 53792

Contacts

UW Carbone Cancer Center - Cancer Connect

800-622-8922clinicaltrials@cancer.wisc.edu

More Information

Sponsor

Kura Oncology, Inc.

Last update posted

Jun 8, 2026

Last verified

Jun, 2026

Keywords

  • HRAS
  • KRAS
  • NRAS
  • Farnesyltransferase inhibitor (FTI)
  • Tyrosine Kinase inhibitor (TKI)
  • Phase 1
  • KRAS G12C inhibitor
  • NSCLC
  • ccRCC
  • RCC
  • PDAC
  • CRC

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Kura Oncology, Inc. on 2026-06-08.