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KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors (FIT-001)

Primary Purpose

Solid Tumors With HRAS Alterations, Non Small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC)

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
KO-2806
Cabozantinib
Sponsored by
Kura Oncology, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Solid Tumors With HRAS Alterations focused on measuring HRAS, KRAS, NRAS, Farnesyl transferase inhibitor (FTI), Tyrosine Kinase inhibitor (TKI), Phase 1

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 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.

Sites / Locations

  • University of Southern CaliforniaRecruiting
  • Dana-Farber Cancer InstituteRecruiting
  • Washington University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm #1: RAS-altered advanced solid tumors

Arm #2: Advanced or metastatic ccRCC

Arm Description

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

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

Outcomes

Primary Outcome Measures

Rate of dose-limiting toxicities (DLTs)
Descriptive statistics of adverse events
NCI-CTCAE v5.0
Overall Response Rate (ORR)
Assessed per RECIST v1.1

Secondary Outcome Measures

Rate of dose-limiting toxicities (DLTs)
Descriptive statistics of adverse events
NCI-CTCAE v5.0
Objective Response Rate (ORR)
Assessed per RECIST v1.1
Disease control rate (DCR)
Assessed per RECIST v1.1
Duration of response (DoR)
Assessed per RECIST v1.1
Progression-Free Survival (PFS)
Assessed per RECIST v1.1
Overall Survival (OS)
Assessed per RECIST v1.1
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.
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
Cmax
Maximum plasma concentration (Cmax) of KO-2806 (in the absence and presence of food) and the combination agent
Tmax
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)
Estimated terminal elimination rate constant of KO-2806 and the combination agent
t1/2
Half-life (t1/2) of KO-2806 (in the absence and presence of food) and the combination agent
CL/F
Oral clearance (CL/F) of KO-2806 and the combination agent
Vd/F
Oral volume of distribution (Vd/F) of KO-2806 and the combination agent
QTcF
QT interval corrected for heart rate (HR) using Fridericia's formula (QTcF) for KO-2806 monotherapy (dose escalation)
KO-2806 plasma concentration measurements
Amount of KO-2806 excretion in urine
CLr of KO-2806 excretion in urine
Renal clearance of KO-2806 excretion in urine
t1/2 of KO-2806 excretion in urine
Half-life of KO-2806 excretion in urine
Relative bioavailability of KO-2806 formulations

Full Information

First Posted
August 17, 2023
Last Updated
October 9, 2023
Sponsor
Kura Oncology, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT06026410
Brief Title
KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 2023 (Anticipated)
Primary Completion Date
January 2027 (Anticipated)
Study Completion Date
April 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kura Oncology, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Solid Tumors With HRAS Alterations, Non Small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC), Pancreatic Ductal Adenocarcinoma (PDAC), Clear Cell Renal Cell Carcinoma (ccRCC)
Keywords
HRAS, KRAS, NRAS, Farnesyl transferase inhibitor (FTI), Tyrosine Kinase inhibitor (TKI), Phase 1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
270 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm #1: RAS-altered advanced solid tumors
Arm Type
Experimental
Arm Description
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 Title
Arm #2: Advanced or metastatic ccRCC
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
KO-2806
Intervention Description
Oral administration
Intervention Type
Drug
Intervention Name(s)
Cabozantinib
Other Intervention Name(s)
Cabometyx
Intervention Description
Oral administration
Primary Outcome Measure Information:
Title
Rate of dose-limiting toxicities (DLTs)
Time Frame
DLTs will be evaluated during the first 28 days of KO-2806 treatment (dose escalation)
Title
Descriptive statistics of adverse events
Description
NCI-CTCAE v5.0
Time Frame
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)
Title
Overall Response Rate (ORR)
Description
Assessed per RECIST v1.1
Time Frame
Up to an estimated period of 24 months (dose expansion)
Secondary Outcome Measure Information:
Title
Rate of dose-limiting toxicities (DLTs)
Time Frame
DLTs will be evaluated during the first 28 days of KO-2806 treatment (dose expansion)
Title
Descriptive statistics of adverse events
Description
NCI-CTCAE v5.0
Time Frame
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)
Title
Objective Response Rate (ORR)
Description
Assessed per RECIST v1.1
Time Frame
Up to an estimated period of 24 months
Title
Disease control rate (DCR)
Description
Assessed per RECIST v1.1
Time Frame
Up to an estimated period of 24 months
Title
Duration of response (DoR)
Description
Assessed per RECIST v1.1
Time Frame
Up to an estimated period of 24 months
Title
Progression-Free Survival (PFS)
Description
Assessed per RECIST v1.1
Time Frame
Up to an estimated period of 24 months
Title
Overall Survival (OS)
Description
Assessed per RECIST v1.1
Time Frame
Up to an estimated period of 24 months
Title
AUClast
Description
Area under the curve from time zero to last measurable concentration for KO-2806 (in the absence and presence of food) and combination agent.
Time Frame
Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
Title
AUC0-inf
Description
Area under the curve from time zero to infinity post administration for KO-2806 (in the absence and presence of food) and combination agent
Time Frame
Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
Title
Cmax
Description
Maximum plasma concentration (Cmax) of KO-2806 (in the absence and presence of food) and the combination agent
Time Frame
Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
Title
Tmax
Description
Time to maximal concentration (Tmax) of KO-2806 (in the absence and presence of food) and the combination agent
Time Frame
Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
Title
Estimated terminal elimination rate constant (λz)
Description
Estimated terminal elimination rate constant of KO-2806 and the combination agent
Time Frame
Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
Title
t1/2
Description
Half-life (t1/2) of KO-2806 (in the absence and presence of food) and the combination agent
Time Frame
Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
Title
CL/F
Description
Oral clearance (CL/F) of KO-2806 and the combination agent
Time Frame
Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
Title
Vd/F
Description
Oral volume of distribution (Vd/F) of KO-2806 and the combination agent
Time Frame
Cycle 1. Each cycle is 28 days. (Dose escalation and dose expansion).
Title
QTcF
Description
QT interval corrected for heart rate (HR) using Fridericia's formula (QTcF) for KO-2806 monotherapy (dose escalation)
Time Frame
Up to day 7 following first dose of KO-2806. Dose escalation.
Title
KO-2806 plasma concentration measurements
Time Frame
Up to day 7 following first dose of KO-2806. Dose escalation.
Title
Amount of KO-2806 excretion in urine
Time Frame
Up to 24 hours following first dose of KO-2806. Dose escalation.
Title
CLr of KO-2806 excretion in urine
Description
Renal clearance of KO-2806 excretion in urine
Time Frame
Up to 24 hours following first dose of KO-2806. Dose escalation.
Title
t1/2 of KO-2806 excretion in urine
Description
Half-life of KO-2806 excretion in urine
Time Frame
Up to 24 hours following first dose of KO-2806. Dose escalation.
Title
Relative bioavailability of KO-2806 formulations
Time Frame
Up to 24 hours following first dose of KO-2806. Dose expansion.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 with predominantly clear cell subtype 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical Operations
Phone
617-588-3755
Email
KO-2806-001@kuraoncology.com
Facility Information:
Facility Name
University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiomara Menendez, RN
Phone
323-865-3000
Email
Xiomara.Menendez@med.usc.edu
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emily McClure, RN
Phone
857-215-0180
Email
Emily_mcclure@dfci.harvard.edu
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jessica Ley
Phone
314-747-8092
Email
jcley@wustl.edu

12. IPD Sharing Statement

Learn more about this trial

KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors

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