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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Cancer; Colorectal Cancer; Lung Cancer; Solid Tumor; Non Small Cell Lung Cancer; Colon Cancer; Cancer of Pancreas
• Intervention / Treatment: Drug: HBI-2438

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• Puerto Rico
  • Puerto Rico
    • Rio Piedras, Puerto Rico, Puerto Rico, 00935
      • Pan American Center for Oncology Trials (PanOncology Trials)
• United States
  • California
    • Encinitas, California, United States, 92024
      • California Cancer Associates for Research and Excellence, Inc. (cCARE)
    • Glendale, California, United States, 91204
      • The Oncology Institute of Hope and Innovation
    • Long Beach, California, United States, 90805
      • The Oncology Institute of Hope and Innovation
    • Pasadena, California, United States, 91105
      • The Oncology Institute of Hope and Innovation
    • San Marcos, California, United States, 92069
      • California Cancer Associates for Research and Excellence, Inc. (cCARE)
    • Santa Ana, California, United States, 92705
      • The Oncology Institute of Hope and Innovation
    • Santa Monica, California, United States, 90403
      • Sarcoma Oncology
    • Whittier, California, United States, 90603
      • The Oncology Institute of Hope and Innovation
    • Whittier, California, United States, 90603
      • Innovative Clinical Research Institute (ICRI)
  • Florida
    • Plantation, Florida, United States, 33322
      • BRCR Medical Center
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Michigan Center of Medical Research
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • Alliance for Multispecialty Research, LLC
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation and Expansion; HBI-2438 will be given orally in ascending doses (escalation cohort), until the maximum tolerated dose or recommended Phase 2 dose is reached. Up to 6-8 patients will then be enrolled in the expansion cohort at the recommended dose.	Drug: HBI-2438; KRAS G12C Inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the maximum tolerated dose (MTD)	Safety endpoints: Incidence of dose-limiting toxicities (DLTs)	Up to 36 months
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
maximum plasma concentration (Cmax)	Pharmacokinetic variables including maximum plasma concentration (Cmax)	Cycle 1 (21 days)
minimum plasma concentration (Cmin)	Pharmacokinetic variables including minimum plasma concentration (Cmin)	Cycle 1 (21 days)
Area Under the Curve (AUC)	Pharmacokinetic variables including Area Under the Curve (AUC)	Cycle 1 (21 days)
Pharmacokinetic variables including clearance	Pharmacokinetic variables including clearance	Cycle 1 (21 days)
Pharmacokinetic variables including serum half-life	Pharmacokinetic variables including serum half-life	Cycle 1 (21 days)
Pharmacokinetic variables including volume of distribution	Pharmacokinetic variables including volume of distribution	Cycle 1 (21 days)

Collaborators and Investigators

• Sponsor: HUYABIO International, LLC.
• Investigators: Principal Investigator: Alberto Bessudo, MD, California Cancer Associates for Research and Excellence, Inc. (cCARE)

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: August 1, 2022
• First Submitted That Met QC Criteria: August 2, 2022
• First Posted (Actual): August 3, 2022

Study Record Updates

• Last Update Posted (Estimated): September 24, 2025
• Last Update Submitted That Met QC Criteria: September 18, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: KRAS G12C; FIH
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Intestinal Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Lung Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplasms; Lung Neoplasms; Colorectal Neoplasms; Colonic Neoplasms; Pancreatic Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: HBI-2438-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No