KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors

NCT06026410 | Recruiting Phase 1 FDA Drug

• 1 other identifier: KO-2806-001
• Study Type: interventional
• Target: 300
• Locations: 5 countries
• Sites: 40

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

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

Keywords

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

Outcome Measures

Primary Outcomes (4)

• Rate of dose-limiting toxicities (DLTs)

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

• Descriptive statistics of adverse events (AEs)

  NCI-CTCAE v5.0

  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

  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)

  Assessed per RECIST v1.1

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

Secondary Outcomes (21)

• Incidence of dose interruptions, reductions, and discontinuations due to AE

  First dose of KO-2806 up to last dose of KO-2806 or up to 24 months of treatment (dose expansion)

• Descriptive statistics of AEs

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

• Objective Response Rate (ORR)

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

• Disease control rate (DCR)

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

• Duration of response (DoR)

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

Study Arms (7)

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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

Drug: Darlifarnib; Drug: Cabozantinib

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

EXPERIMENTAL

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; Drug: Adagrasib

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

EXPERIMENTAL

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

Drug: Darlifarnib; Drug: Cabozantinib

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

EXPERIMENTAL

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

Drug: Cabozantinib

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

EXPERIMENTAL

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

Drug: Darlifarnib; Drug: Cabozantinib

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

EXPERIMENTAL

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

Drug: Darlifarnib; Drug: Adagrasib

Interventions

Adagrasib DRUG

Oral administration

Also known as: Krazati

Arm #3: Advanced or metastatic NSCLC, CRC, or PDAC, combination therapy (escalation phase); Arm #7: Advanced or metastatic NSCLC, combination therapy (expansion phase)

Darlifarnib DRUG

Oral administration

Also known as: KO-2806

Arm #1: RAS-altered advanced solid tumors, monotherapy (escalation phase); Arm #2: Advanced or metastatic RCC, combination therapy (escalation phase); Arm #3: Advanced or metastatic NSCLC, CRC, or PDAC, combination therapy (escalation phase); Arm #4: Advanced or metastatic ccRCC, combination therapy (expansion phase); Arm #6: Advanced or metastatic ccRCC, cabozantinib rollover to combination therapy (expansion phase); Arm #7: Advanced or metastatic NSCLC, combination therapy (expansion phase)

Cabozantinib DRUG

Oral administration

Also known as: Cabometyx

Arm #2: Advanced or metastatic RCC, combination therapy (escalation phase); Arm #4: Advanced or metastatic ccRCC, combination therapy (expansion phase); Arm #5: Advanced or metastatic ccRCC, monotherapy (expansion phase); Arm #6: Advanced or metastatic ccRCC, cabozantinib rollover to combination therapy (expansion phase)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kura Oncology, Inc.: lead
• Mirati Therapeutics Inc.: collaborator

Study Sites (40)

Mayo Clinic Comprehensive Cancer Center

Phoenix, Arizona, 85054, United States

RECRUITING

University of Arizona

Tucson, Arizona, 85721, United States

RECRUITING

University of Arizona

Tucson, Arizona, 85724, United States

RECRUITING

University of Southern California

Los Angeles, California, 90033, United States

RECRUITING

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

UCLA Department of Medicine

Los Angeles, California, 90095, United States

RECRUITING

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218, United States

RECRUITING

AdventHealth Celebration

Celebration, Florida, 34747, United States

RECRUITING

Mayo Clinic Comprehensive Cancer Center

Jacksonville, Florida, 32224, United States

RECRUITING

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

RECRUITING

University of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Henry Ford Health System

Detroit, Michigan, 48202, United States

RECRUITING

Mayo Clinic Comprehensive Cancer Center

Rochester, Minnesota, 55905, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

RECRUITING

Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

OU Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

SCRI - Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

UT Southwestern Simmons Cancer Center

Dallas, Texas, 75235, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

University of Wisconsin (Carbone Cancer Center)

Madison, Wisconsin, 53792, United States

RECRUITING

Centre Leon Berard

Lyon, 69495, France

RECRUITING

Oncologie médicale - Pitié-Salpêtrière

Paris, 75013, France

RECRUITING

Hopital Européen Georges Pompidou

Paris, 75015, France

RECRUITING

Institut Universitaire du Cancer Toulouse - Oncopole

Toulouse, 31059, France

RECRUITING

Charité - Universitätsmedizin Berlin

Berlin, 10117, Germany

RECRUITING

Charité - Universitätsmedizin Berlin

Berlin, 12203, Germany

RECRUITING

Universitätsklinikum Ulm

Ulm, 89081, Germany

RECRUITING

Universitätsklinikum Würzburg

Würzburg, 97080, Germany

RECRUITING

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS

Bologna, 40138, Italy

RECRUITING

Fondazione Piemonte per l'Oncologia - IRCCs Candiolo

Candiolo, 10060, Italy

RECRUITING

Istituto Nazionale Tumori IRCCS

Naples, 80131, Italy

RECRUITING

Humanitas University

Rozzano, 20089, Italy

RECRUITING

AOU Verona - Centro Ricerche Cliniche di Verona

Verona, 37134, Italy

RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Hospital de la Santa Creu i de Sant Pau

Barcelona, 08041, Spain

RECRUITING

Hospital HM Sanchinarro START Madrid-CIOCC

Madrid, 28050, Spain

RECRUITING

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Carcinoma, Renal Cell; Kidney Neoplasms

Interventions

cabozantinib; adagrasib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Central Study Contacts

Kura Medical Information

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2023
• First Posted: September 7, 2023
• Study Start: October 18, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: April 14, 2026

Record last verified: 2026-04

Locations

US (23); FR (4); DE (4); IT (5); ES (4)