KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors

Phase 1RecruitingNCT06026410

Kura Oncology, Inc.300 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

300

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

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (32)

Mayo Clinic Comprehensive Cancer Center

Phoenix, Arizona, United States

RECRUITING

University of Southern California

Los Angeles, California, United States

RECRUITING

Cedars-Sinai Medical Center

Los Angeles, California, United States

RECRUITING

UCLA Department of Medicine

Los Angeles, California, United States

Outcomes

Primary Outcomes

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)

NCI-CTCAE v5.0

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)

Assessed per RECIST v1.1

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

Secondary Outcomes

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 expansion)

Descriptive statistics of AEs

NCI-CTCAE v5.0

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

Objective Response Rate (ORR)

Assessed per RECIST v1.1

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

Disease control rate (DCR)

Assessed per RECIST v1.1

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

Duration of response (DoR)

Assessed per RECIST v1.1

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

Time to response (TTR)

Assessed per RECIST v1.1

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

Progression-Free Survival (PFS)

Assessed per RECIST v1.1

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

Overall Survival (OS)

For patients with no events, OS will be censored at the last known to be alive date

Time frame: First dose of KO-2806 until death, or up to an estimated period of 37 months (dose escalation and expansion)

AUClast

Area under the curve from time zero to last measurable concentration for KO-2806 (in the absence and presence of food) and combination agent.