Back to resultsA Dose Escalation Study of SHP2 Inhibitor in Patients With Solid Tumors Harboring KRAS of EGFR Mutations
Primary Purpose
Non Small Cell Lung Cancer, Colorectal Cancer, Pancreatic Cancer
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
HBI-2376
Sponsored by
About this trial
This is an interventional treatment trial for Non Small Cell Lung Cancer focused on measuring KRAS, EGFR, SHP2, FIH
Eligibility Criteria
Key Inclusion Criteria:
- Male or female at least 18 years of age at the time of signing the ICF prior to initiation of any study specific activities/procedures
- Advanced malignant solid tumors with KRAS or EGFR mutations diagnosed by histology or cytology
- Relapsed or refractory to, or intolerant of, or refuse approved or standard of care established therapy known to provide clinical benefit for disease
- At least 1 measurable target lesion that meets the definition of RECIST v1.1
- ECOG Performance Status of 0 or 1
- Demonstrate adequate organ function
- Must be able to swallow oral medications and must not have gastrointestinal abnormalities that significantly affect drug absorption
Key Exclusion Criteria:
- History of another concurrent malignancy within 3 years prior to study entry, unless the malignancy was treated with curative intent and the likelihood of relapse is <5% in 2 years Note: Subjects with a history of squamous or basal cell carcinoma of the skin or carcinoma in the situ of the cervix may be enrolled
- Untreated or symptomatic central nervous system (CNS) metastases Note: Subjects with asymptomatic treated CNS metastases are eligible provided they have been clinically stable and not requiring steroids for at least 4 weeks
- Clinically significant cardiovascular disease, including stroke or myocardial infarction within 6 months
- Any unresolved Grade 2 or greater toxicity from previous anti-cancer therapy, except alopecia, within 4 weeks of first study treatment administration
- Active autoimmune diseases or history of autoimmune diseases that may relapse
- Pregnant or nursing
- Prior treatment with any SHP2 inhibitors
- Any condition that required systemic treatment with either corticosteroids (>10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤14 days before the first study treatment administration
- Treatment with other investigational drugs/devices within 4 weeks prior to first study treatment administration
Sites / Locations
- City of HopeRecruiting
- California Cancer Associates for Research and Excellence, Inc. (cCare)Recruiting
- Providence Medical FoundationRecruiting
- California Cancer Associates for Research and Excellence, Inc. (cCare)Recruiting
- Sarcoma OncologyRecruiting
- UCLA Hematology/OncologyRecruiting
- Orlando Health, Inc.Recruiting
- BRCR Medical CenterRecruiting
- Gabrail Cancer CenterRecruiting
- Texas Oncology - TylerRecruiting
- Virginia Cancer SpecialistsRecruiting
- Pan American Center for Oncology Trials (PanOncology Trials)Recruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Dose Escalation and Expansion
Arm Description
HBI-2376 will be given orally in ascending doses (escalation cohort), until the maximum tolerated dose or recommended Phase 2 dose is reached. Up to 6 patients will then be enrolled in the expansion cohort at the recommended dose.
Outcomes
Primary Outcome Measures
To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), of HBI-2376 as an oral monotherapy for advanced solid tumors harboring KRAS or EGFR mutations.
Safety endpoints: Incidence of dose-limiting toxicities (DLTs), adverse events (AEs), and serious adverse events (SAEs) overall, by severity, by relationship to HBI-2376, and those that led to discontinuation of HBI-2376
Secondary Outcome Measures
Pharmacokinetic variables including maximum plasma concentration (Cmax)
Pharmacokinetic variables including maximum plasma concentration (Cmax)
Pharmacokinetic variables including minimum plasma concentration (Cmin)
Pharmacokinetic variables including minimum plasma concentration (Cmin)
Pharmacokinetic variables including Area Under the Curve (AUC)
Pharmacokinetic variables including Area Under the Curve (AUC)
Pharmacokinetic variables including clearance
Pharmacokinetic variables including clearance
Pharmacokinetic variables including serum half-life
Pharmacokinetic variables including serum half-life
Pharmacokinetic variables including volume of distribution
Pharmacokinetic variables including volume of distribution
Full Information
NCT ID
NCT05163028
First Posted
November 24, 2021
Last Updated
September 12, 2023
Sponsor
HUYABIO International, LLC.
1. Study Identification
Unique Protocol Identification Number
NCT05163028
Brief Title
A Dose Escalation Study of SHP2 Inhibitor in Patients With Solid Tumors Harboring KRAS of EGFR Mutations
Official Title
A Phase 1, Open-Label, Dose Escalation of HBI-2376 in Patients With Advanced Malignant Solid Tumors Harboring KRAS or EGFR Mutations
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 13, 2021 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
HUYABIO International, LLC.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A Phase 1 dose escalation study in patients with advanced solid tumors harboring KRAS or EGFR mutations to determine the maximum tolerated dose and recommended Phase II dose of HBI-2376 and characterize its pharmacokinetic profile.
Detailed Description
A Phase 1, Open-Label, Dose Escalation of HBI-2376 in Patients with Advanced Malignant Solid Tumors Harboring KRAS or EGFR Mutations. The primary and secondary objectives are:
To determine the MTD and recommended Phase 2 dose (RP2D), of HBI-2376 as an oral monotherapy for advanced solid tumors harboring KRAS or EGFR mutations
To characterize the PK of HBI-2376 in subjects with advanced malignant solid tumors harboring KRAS or EGFR mutations
HBI-2376 is a SHP2 Inhibitor and will be dosed once daily throughout the escalation and expansion phase. Up to 42 subjects will be enrolled sequentially into the 3+3 dose escalation and monitored throughout the study for safety and tolerability. The dose escalation phase will consist of 6 cohorts, with doses ranging from 6 to 40mg. Once the MTD of RP2D is established, additional 6 subjects will be enrolled into the expansion phase at that dose level.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Small Cell Lung Cancer, Colorectal Cancer, Pancreatic Cancer, Solid Tumor, Cancer, Cancer of Pancreas, Cancer of Colon
Keywords
KRAS, EGFR, SHP2, FIH
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
3+3 Dose Escalation Design with Expansion
Masking
None (Open Label)
Allocation
N/A
Enrollment
42 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dose Escalation and Expansion
Arm Type
Experimental
Arm Description
HBI-2376 will be given orally in ascending doses (escalation cohort), until the maximum tolerated dose or recommended Phase 2 dose is reached. Up to 6 patients will then be enrolled in the expansion cohort at the recommended dose.
Intervention Type
Drug
Intervention Name(s)
HBI-2376
Intervention Description
SHP2 Inhibitor
Primary Outcome Measure Information:
Title
To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), of HBI-2376 as an oral monotherapy for advanced solid tumors harboring KRAS or EGFR mutations.
Description
Safety endpoints: Incidence of dose-limiting toxicities (DLTs), adverse events (AEs), and serious adverse events (SAEs) overall, by severity, by relationship to HBI-2376, and those that led to discontinuation of HBI-2376
Time Frame
Up to 36 months
Secondary Outcome Measure Information:
Title
Pharmacokinetic variables including maximum plasma concentration (Cmax)
Description
Pharmacokinetic variables including maximum plasma concentration (Cmax)
Time Frame
Cycle 1 (28 days)
Title
Pharmacokinetic variables including minimum plasma concentration (Cmin)
Description
Pharmacokinetic variables including minimum plasma concentration (Cmin)
Time Frame
Cycle 1 (28 days)
Title
Pharmacokinetic variables including Area Under the Curve (AUC)
Description
Pharmacokinetic variables including Area Under the Curve (AUC)
Time Frame
Cycle 1 (28 days)
Title
Pharmacokinetic variables including clearance
Description
Pharmacokinetic variables including clearance
Time Frame
Cycle 1 (28 days)
Title
Pharmacokinetic variables including serum half-life
Description
Pharmacokinetic variables including serum half-life
Time Frame
Cycle 1 (28 days)
Title
Pharmacokinetic variables including volume of distribution
Description
Pharmacokinetic variables including volume of distribution
Time Frame
Cycle 1 (28 days)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Male or female at least 18 years of age at the time of signing the ICF prior to initiation of any study specific activities/procedures
Advanced malignant solid tumors with KRAS or EGFR mutations diagnosed by histology or cytology
Relapsed or refractory to, or intolerant of, or refuse approved or standard of care established therapy known to provide clinical benefit for disease
At least 1 measurable target lesion that meets the definition of RECIST v1.1
ECOG Performance Status of 0 or 1
Demonstrate adequate organ function
Must be able to swallow oral medications and must not have gastrointestinal abnormalities that significantly affect drug absorption
Key Exclusion Criteria:
History of another concurrent malignancy within 3 years prior to study entry, unless the malignancy was treated with curative intent and the likelihood of relapse is <5% in 2 years Note: Subjects with a history of squamous or basal cell carcinoma of the skin or carcinoma in the situ of the cervix may be enrolled
Untreated or symptomatic central nervous system (CNS) metastases Note: Subjects with asymptomatic treated CNS metastases are eligible provided they have been clinically stable and not requiring steroids for at least 4 weeks
Clinically significant cardiovascular disease, including stroke or myocardial infarction within 6 months
Any unresolved Grade 2 or greater toxicity from previous anti-cancer therapy, except alopecia, within 4 weeks of first study treatment administration
Active autoimmune diseases or history of autoimmune diseases that may relapse
Pregnant or nursing
Prior treatment with any SHP2 inhibitors
Any condition that required systemic treatment with either corticosteroids (>10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤14 days before the first study treatment administration
Treatment with other investigational drugs/devices within 4 weeks prior to first study treatment administration
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
John Ning, MD,PhD,FAIC
Phone
858-280-1866
Email
jning@huyabio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ravi Salgia, MD
Organizational Affiliation
City of Hope Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Susan Hmwe
Phone
626-218-4404
Email
shmwe@coh.org
First Name & Middle Initial & Last Name & Degree
Ravi Salgia, MD
Facility Name
California Cancer Associates for Research and Excellence, Inc. (cCare)
City
Encinitas
State/Province
California
ZIP/Postal Code
92024
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christina Spencer
Phone
760-452-3909
Email
cspencer@ccare.com
First Name & Middle Initial & Last Name & Degree
Alberto Bessudo, MD
Facility Name
Providence Medical Foundation
City
Fullerton
State/Province
California
ZIP/Postal Code
92835
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Noli Raz
Phone
717-446-5642
Email
Noli.Raz@stjoe.org
First Name & Middle Initial & Last Name & Degree
David J Park, MD
Facility Name
California Cancer Associates for Research and Excellence, Inc. (cCare)
City
San Marcos
State/Province
California
ZIP/Postal Code
92069
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christina Spencer
Phone
760-452-3909
Email
cspencer@ccare.com
First Name & Middle Initial & Last Name & Degree
Alberto Bessudo, MD
Facility Name
Sarcoma Oncology
City
Santa Monica
State/Province
California
ZIP/Postal Code
90403
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Victoria S Chua-Alcala, MD, CLS
Phone
310-552-9999
Email
vchua@sarcomaoncology.com
First Name & Middle Initial & Last Name & Degree
Sant Chawla, MD
Facility Name
UCLA Hematology/Oncology
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joanna Gutierrez
Phone
310-633-8400
Ext
16370
Email
mailto:JGGutierrez@mednet.ucla.edu
First Name & Middle Initial & Last Name & Degree
Jonathan Goldman, MD
Facility Name
Orlando Health, Inc.
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kiera Grofsik
Phone
321-841-6626
Email
kiera.grofsik@orlandohealth.com
First Name & Middle Initial & Last Name & Degree
Sajeve Thomas, MD
Facility Name
BRCR Medical Center
City
Plantation
State/Province
Florida
ZIP/Postal Code
33322
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ines Padron
Phone
561-447-0614
Ext
102
Email
ipadron@brcrglobal.com
First Name & Middle Initial & Last Name & Degree
Harshad Amin, MD
Facility Name
Gabrail Cancer Center
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kim Roby
Phone
330-492-3345
Ext
227
Email
kroby@gabrailcancercenter.com
First Name & Middle Initial & Last Name & Degree
Nashat Gabrail, MD
Facility Name
Texas Oncology - Tyler
City
Tyler
State/Province
Texas
ZIP/Postal Code
75702
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Penny Watkins, RN
Phone
903-579-9800
Email
penny.watkins@usoncology.com
First Name & Middle Initial & Last Name & Degree
Donald A Richards, MD, PhD
Facility Name
Virginia Cancer Specialists
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cynthia DeLeon
Phone
210-580-9521
Email
cdeleon@nextoncology.com
First Name & Middle Initial & Last Name & Degree
Alexander Spira, MD, PhD
Facility Name
Pan American Center for Oncology Trials (PanOncology Trials)
City
Rio Piedras
ZIP/Postal Code
00935
Country
Puerto Rico
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marcia R Cruz-Correa, MD,PhD,AGAF,FASGE
Phone
787-407-3333
Email
marcia.cruzcorrea@panoncologytrials.com
First Name & Middle Initial & Last Name & Degree
Marcia R Cruz-Correa, MD,PhD,AGAF,FASGE
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Dose Escalation Study of SHP2 Inhibitor in Patients With Solid Tumors Harboring KRAS of EGFR Mutations
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