KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors

Non Small Cell Lung Cancer (NSCLC) Clinical Trial

— FIT-001  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06026410
• Other study ID #: KO-2806-001
• Status: Recruiting
• Phase: Phase 1
• Start date: October 18, 2023
• Est. completion date: April 2027

Study information

• Verified date: April 2024
• Source: Kura Oncology, Inc.
• Contact: Clinical Operations
• Phone: 617-588-3755
• Email: KO-2806-001[@]kuraoncology.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 270
• Est. completion date: April 2027
• Est. primary completion date: January 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 with predominantly clear cell subtype
• Arm #3 (Combination): Must have KRAS G12C-mutant locally advanced or metastatic NSCLC and have received at least 1 prior systemic therapy for 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:

• 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.

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Clear Cell Renal Cell Carcinoma (ccRCC)
• Colorectal Cancer (CRC)
• Non Small Cell Lung Cancer (NSCLC)
• Pancreatic Ductal Adenocarcinoma (PDAC)

Intervention

Drug:
• KO-2806
Oral administration
• Cabozantinib
Oral administration
• Adagrasib
Oral administration

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	AdventHealth Celebration	Celebration	Florida
United States	Sarah Cannon Research Institute at HealthONE	Denver	Colorado
United States	UCLA Department of Medicine	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	University of Wisconsin (Carbone Cancer Center)	Madison	Wisconsin
United States	SCRI - Oncology Partners	Nashville	Tennessee
United States	OU Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Florida Cancer Specialists	Sarasota	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Kura Oncology, Inc.	Mirati Therapeutics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of dose-limiting toxicities (DLTs)		DLTs will be evaluated during the first 28 days of KO-2806 treatment (dose escalation)
Primary	Descriptive statistics of adverse events	NCI-CTCAE v5.0	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)
Primary	Overall Response Rate (ORR)	Assessed per RECIST v1.1	Up to an estimated period of 24 months (dose expansion)
Secondary	Rate of dose-limiting toxicities (DLTs)		DLTs will be evaluated during the first 28 days of KO-2806 treatment (dose expansion)
Secondary	Descriptive statistics of adverse events	NCI-CTCAE v5.0	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)
Secondary	Objective Response Rate (ORR)	Assessed per RECIST v1.1	Up to an estimated period of 24 months (dose escalation)
Secondary	Disease control rate (DCR)	Assessed per RECIST v1.1	Up to an estimated period of 24 months (dose escalation and expansion)
Secondary	Duration of response (DoR)	Assessed per RECIST v1.1	Up to an estimated period of 24 months (dose escalation and expansion)
Secondary	Progression-Free Survival (PFS)	Assessed per RECIST v1.1	Up to an estimated period of 24 months (dose escalation and expansion)
Secondary	Overall Survival (OS)	Assessed per RECIST v1.1	Up to an estimated period of 24 months (dose escalation and expansion)
Secondary	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.	Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
Secondary	AUC0-inf	Area under the curve from time zero to infinity post administration for KO-2806 (in the absence and presence of food) and combination agent	Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
Secondary	Cmax	Maximum plasma concentration (Cmax) of KO-2806 (in the absence and presence of food) and the combination agent	Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
Secondary	Cmin	Minimum plasma concentration (Cmin) of KO-2806 (in the absence and presence of food) and the combination agent	Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
Secondary	Tmax	Time to maximal concentration (Tmax) of KO-2806 (in the absence and presence of food) and the combination agent	Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
Secondary	Estimated terminal elimination rate constant (?z)	Estimated terminal elimination rate constant of KO-2806 and the combination agent	Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
Secondary	t1/2	Half-life (t1/2) of KO-2806 (in the absence and presence of food) and the combination agent	Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
Secondary	CL/F	Total apparent clearance (CL/F) of KO-2806 and the combination agent	Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
Secondary	Vd/F	Total apparent volume of distribution (Vd/F) of KO-2806 and the combination agent	Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
Secondary	QTcF	QT interval corrected for heart rate (HR) using Fridericia's formula (QTcF) for KO-2806 monotherapy and in combination	Up to day 7 following first dose of KO-2806 and adagrasib. Dose escalation.
Secondary	KO-2806 plasma concentration measurements		Up to day 28 following first dose of KO-2806 and adagrasib. Dose escalation.
Secondary	Amount of KO-2806 excretion in urine		Up to 24 hours following first dose of KO-2806. Dose escalation.
Secondary	CLr of KO-2806 excretion in urine	Renal clearance of KO-2806 excretion in urine	Up to 24 hours following first dose of KO-2806. Dose escalation.