A Dose Escalation Study of HBI-2438 in Patients With Solid Tumors Harboring KRAS G12C Mutation

Cancer Clinical Trial

Official title:

A Phase 1, Open Label, Dose Escalation of HBI-2438 in Patients With Advanced Malignant Solid Tumors Harboring KRAS G12C Mutation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05485974
• Other study ID #: HBI-2438-101
• Status: Recruiting
• Phase: Phase 1
• Start date: August 1, 2022
• Est. completion date: August 2025

Study information

• Verified date: September 2023
• Source: HUYABIO International, LLC.
• Contact: John Ning, MD,PhD,FAIC
• Phone: 858-280-1866
• Email: jning[@]huyabio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Phase 1 dose escalation study in patients with advanced solid tumors harboring KRAS G12C mutation to determine the maximum tolerated dose and recommended Phase II dose of HBI-2438 and characterize its pharmacokinetic profile.

Description:

A Phase 1, Open-Label, Dose Escalation of HBI-2438 in Patients with Advanced Malignant Solid Tumors Harboring KRAS G12C Mutation. The primary and secondary objectives are:

1. To determine the MTD and recommended Phase 2 dose (RP2D) of HBI-2438 as an oral monotherapy for advanced solid tumors harboring KRAS G12C mutation.

2. To characterize the PK of HBI-2438 in subjects with advanced malignant solid tumors harboring KRAS G12C mutation.

HBI-2438 is an orally administered KRAS G12C Inhibitor and will be dosed once daily throughout the escalation and expansion phase. Up to 44 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 150 to 1200mg. Once the MTD of RP2D is established, an additional 6-8 subjects with brain metastases will be enrolled into the expansion phase at that dose level.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 44
• Est. completion date: August 2025
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion 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 G12C mutation- as determined by genetic testing

Must have failed or refused standard of care therapy, are not eligible for standard of care therapy, or cannot benefit from standard of care therapy, in the opinion of the Investigator

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

Expected survival time > 3 months in the opinion of the investigator

Must be able to swallow oral medications and must not have gastrointestinal abnormalities that significantly affect drug absorption

Exclusion Criteria:

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 prior to first dose of HBI-2438; or the presence of unstable angina or congestive heart failure of New York Heart Association Grade 2 or higher

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 KRAS G12C 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

Related Conditions & MeSH terms

• Cancer
• Cancer of Pancreas
• Colon Cancer
• Colorectal Cancer
• Lung Cancer
• Lung Neoplasms
• Non Small Cell Lung Cancer
• Pancreatic Neoplasms
• Solid Tumor

Intervention

Drug:
• HBI-2438
KRAS G12C Inhibitor

Locations

Country	Name	City	State
Puerto Rico	Pan American Center for Oncology Trials (PanOncology Trials)	Rio Piedras
United States	Gabrail Cancer Center	Canton	Ohio
United States	California Cancer Associates for Research and Excellence, Inc. (cCare)	Encinitas	California
United States	Michigan Center of Medical Research	Farmington Hills	Michigan
United States	The Oncology Institute of Hope and Innovation	Glendale	California
United States	Alliance for Multispecialty Research, LLC	Kansas City	Missouri
United States	The Oncology Institute of Hope and Innovation	Long Beach	California
United States	The Oncology Institute of Hope and Innovation	Pasadena	California
United States	BRCR Medical Center	Plantation	Florida
United States	California Cancer Associates for Research and Excellence, Inc. (cCare)	San Marcos	California
United States	The Oncology Institute of Hope and Innovation	Santa Ana	California
United States	Sarcoma Oncology	Santa Monica	California
United States	Innovative Clinical Research Institute (ICRI)	Whittier	California
United States	The Oncology Institute of Hope and Innovation	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
HUYABIO International, LLC.

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the maximum tolerated dose (MTD)	Safety endpoints: Incidence of dose-limiting toxicities (DLTs)	Up to 36 months
Primary	adverse events (AEs), and serious adverse events (SAEs) overall	Safety endpoints: adverse events (AEs), and serious adverse events (SAEs) overall	Up to 36 months
Secondary	maximum plasma concentration (Cmax)	Pharmacokinetic variables including maximum plasma concentration (Cmax)	Cycle 1 (21 days)
Secondary	minimum plasma concentration (Cmin)	Pharmacokinetic variables including minimum plasma concentration (Cmin)	Cycle 1 (21 days)
Secondary	Area Under the Curve (AUC)	Pharmacokinetic variables including Area Under the Curve (AUC)	Cycle 1 (21 days)
Secondary	Pharmacokinetic variables including clearance	Pharmacokinetic variables including clearance	Cycle 1 (21 days)
Secondary	Pharmacokinetic variables including serum half-life	Pharmacokinetic variables including serum half-life	Cycle 1 (21 days)
Secondary	Pharmacokinetic variables including volume of distribution	Pharmacokinetic variables including volume of distribution	Cycle 1 (21 days)