KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors
- Conditions
- Solid Tumors With HRAS AlterationsNon Small Cell Lung Cancer (NSCLC)Colorectal Cancer (CRC)Pancreatic Ductal Adenocarcinoma (PDAC)Clear Cell Renal Cell Carcinoma (ccRCC)Renal Cell Carcinoma (Kidney Cancer)
- Interventions
- Registration Number
- NCT06026410
- Lead Sponsor
- Kura Oncology, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 270
-
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
- Arm #3 (Combination): Must have KRAS G12C-mutant locally advanced or metastatic NSCLC, CRC, or PDAC and have received at least 1 prior systemic therapy for advanced or metastatic disease
-
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.
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Arm #1: RAS-altered advanced solid tumors KO-2806 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 Arm #2: Advanced or metastatic RCC KO-2806 Patients who have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic RCC Arm #2: Advanced or metastatic RCC Cabozantinib Patients who have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic RCC Arm #3: Advanced or metastatic NSCLC, CRC, or PDAC KO-2806 Patients with KRAS G12C-mutant locally advanced or metastatic NSCLC, CRC, or PDAC who have received at least 1 prior systemic therapy for advanced or metastatic disease Arm #3: Advanced or metastatic NSCLC, CRC, or PDAC Adagrasib Patients with KRAS G12C-mutant locally advanced or metastatic NSCLC, CRC, or PDAC who have received at least 1 prior systemic therapy for advanced or metastatic disease
- Primary Outcome Measures
Name Time Method 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 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
Overall Response Rate (ORR) Up to an estimated period of 24 months (dose expansion) Assessed per RECIST v1.1
- Secondary Outcome Measures
Name Time Method Rate of dose-limiting toxicities (DLTs) DLTs will be evaluated during the first 28 days of KO-2806 treatment (dose expansion) Descriptive statistics of adverse events 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
Objective Response Rate (ORR) Up to an estimated period of 24 months (dose escalation) Assessed per RECIST v1.1
Disease control rate (DCR) Up to an estimated period of 24 months (dose escalation and expansion) Assessed per RECIST v1.1
Duration of response (DoR) Up to an estimated period of 24 months (dose escalation and expansion) Assessed per RECIST v1.1
Progression-Free Survival (PFS) Up to an estimated period of 24 months (dose escalation and expansion) Assessed per RECIST v1.1
Overall Survival (OS) Up to an estimated period of 24 months (dose escalation and expansion) Assessed per RECIST v1.1
AUClast 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.
AUC0-inf 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
Cmax 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
Cmin 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
Tmax 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
Estimated terminal elimination rate constant (λz) Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion). Estimated terminal elimination rate constant of KO-2806 and the combination agent
t1/2 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
CL/F Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion). Total apparent clearance (CL/F) of KO-2806 and the combination agent
Vd/F 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
QTcF Up to day 7 following first dose of KO-2806 and adagrasib. Dose escalation and dose expansion. QT interval corrected for heart rate (HR) using Fridericia's formula (QTcF) for KO-2806 monotherapy and in combination
KO-2806 plasma concentration measurements Up to day 28 following first dose of KO-2806 and adagrasib. Dose escalation and dose expansion. Amount of KO-2806 excretion in urine Up to 24 hours following first dose of KO-2806. Dose escalation. CLr of KO-2806 excretion in urine Up to 24 hours following first dose of KO-2806. Dose escalation. Renal clearance of KO-2806 excretion in urine
Trial Locations
- Locations (14)
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
UCLA Department of Medicine
🇺🇸Los Angeles, California, United States
Sarah Cannon Research Institute at HealthONE
🇺🇸Denver, Colorado, United States
AdventHealth Celebration
🇺🇸Celebration, Florida, United States
Florida Cancer Specialists
🇺🇸Sarasota, Florida, United States
University of Iowa Hospitals & Clinics
🇺🇸Iowa City, Iowa, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
OU Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
SCRI - Oncology Partners
🇺🇸Nashville, Tennessee, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Wisconsin (Carbone Cancer Center)
🇺🇸Madison, Wisconsin, United States