Clinical trial NCT06026410: KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors
Official title: Phase 1, First-in-Human, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of KO-2806 When Administered as Monotherapy and in Combination Therapy in Adult Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
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)
Keywords: HRAS
KRAS
NRAS
Farnesyl transferase inhibitor (FTI)
Tyrosine Kinase inhibitor (TKI)
Phase 1
KRAS G12C inhibitor
NSCLC
ccRCC
RCC
PDAC
CRC
Lead sponsor: Kura Oncology, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Mirati Therapeutics Inc.
First posted: 2023-09-07
Enrollment: 270
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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): 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.

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.

Primary outcomes:
measure: Rate of dose-limiting toxicities (DLTs)
timeFrame: DLTs will be evaluated during the first 28 days of KO-2806 treatment (dose escalation)
measure: Descriptive statistics of adverse events
timeFrame: 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)
measure: Overall Response Rate (ORR)
timeFrame: Up to an estimated period of 24 months (dose expansion)
Secondary outcomes:
measure: Rate of dose-limiting toxicities (DLTs)
timeFrame: DLTs will be evaluated during the first 28 days of KO-2806 treatment (dose expansion)
measure: Descriptive statistics of adverse events
timeFrame: 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)
measure: Objective Response Rate (ORR)
timeFrame: Up to an estimated period of 24 months (dose escalation)
measure: Disease control rate (DCR)
timeFrame: Up to an estimated period of 24 months (dose escalation and expansion)
measure: Duration of response (DoR)
timeFrame: Up to an estimated period of 24 months (dose escalation and expansion)
measure: Progression-Free Survival (PFS)
timeFrame: Up to an estimated period of 24 months (dose escalation and expansion)
measure: Overall Survival (OS)
timeFrame: Up to an estimated period of 24 months (dose escalation and expansion)
measure: AUClast
timeFrame: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
measure: AUC0-inf
timeFrame: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
measure: Cmax
timeFrame: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
measure: Cmin
timeFrame: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
measure: Tmax
timeFrame: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
measure: Estimated terminal elimination rate constant (λz)
timeFrame: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
measure: t1/2
timeFrame: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
measure: CL/F
timeFrame: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
measure: Vd/F
timeFrame: Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
measure: QTcF
timeFrame: Up to day 7 following first dose of KO-2806 and adagrasib. Dose escalation and dose expansion.
measure: KO-2806 plasma concentration measurements
timeFrame: Up to day 28 following first dose of KO-2806 and adagrasib. Dose escalation and dose expansion.
measure: Amount of KO-2806 excretion in urine
timeFrame: Up to 24 hours following first dose of KO-2806. Dose escalation.
measure: CLr of KO-2806 excretion in urine
timeFrame: Up to 24 hours following first dose of KO-2806. Dose escalation.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA Department of Medicine
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthONE
state: Colorado
city: Celebration
country: United States
facility: AdventHealth Celebration
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics
state: Iowa
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Oklahoma City
country: United States
facility: OU Stephenson Cancer Center
state: Oklahoma
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: SCRI - Oncology Partners
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Simmons Cancer Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Madison
country: United States
facility: University of Wisconsin (Carbone Cancer Center)
state: Wisconsin
city: Paris
country: France
facility: Oncologie médicale - Pitié-Salpêtrière
city: Paris
country: France
facility: Hopital Européen Georges Pompidou
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS
city: Candiolo
country: Italy
facility: Fondazione Piemonte per l'Oncologia - IRCCs Candiolo
city: Verona
country: Italy
facility: AOU Verona - Centro Ricerche Cliniche di Verona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i de Sant Pau
city: Madrid
country: Spain
facility: Hospital HM Sanchinarro START Madrid-CIOCC
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
Study officials:
References: