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

NCT05485974 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HBI-2438-101
• Study Type: interventional
• Target: 44
• Locations: 2 countries
• Sites: 14

Brief 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.

Conditions

Lung Cancer; Non Small Cell Lung Cancer; Colorectal Cancer; Cancer of Pancreas; Colon Cancer; Solid Tumor; Cancer

Keywords

KRAS G12C; FIH

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• maximum plasma concentration (Cmax)

  Cycle 1 (21 days)

• minimum plasma concentration (Cmin)

  Cycle 1 (21 days)

• Area Under the Curve (AUC)

  Cycle 1 (21 days)

• Pharmacokinetic variables including clearance

  Cycle 1 (21 days)

• Pharmacokinetic variables including serum half-life

  Cycle 1 (21 days)

Study Arms (1)

Dose Escalation and Expansion

EXPERIMENTAL

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

Interventions

HBI-2438 DRUG

KRAS G12C Inhibitor

Dose Escalation and Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• HUYABIO International, LLC.: lead

Study Sites (14)

California Cancer Associates for Research and Excellence, Inc. (cCare)

Encinitas, California, 92024, United States

Location

The Oncology Institute of Hope and Innovation

Glendale, California, 91204, United States

Location

The Oncology Institute of Hope and Innovation

Long Beach, California, 90805, United States

Location

The Oncology Institute of Hope and Innovation

Pasadena, California, 91105, United States

Location

California Cancer Associates for Research and Excellence, Inc. (cCare)

San Marcos, California, 92069, United States

Location

The Oncology Institute of Hope and Innovation

Santa Ana, California, 92705, United States

Location

Sarcoma Oncology

Santa Monica, California, 90403, United States

Location

Innovative Clinical Research Institute (ICRI)

Whittier, California, 90603, United States

Location

The Oncology Institute of Hope and Innovation

Whittier, California, 90603, United States

Location

BRCR Medical Center

Plantation, Florida, 33322, United States

Location

Michigan Center of Medical Research

Farmington Hills, Michigan, 48334, United States

Location

Alliance for Multispecialty Research, LLC

Kansas City, Missouri, 64114, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Pan American Center for Oncology Trials (PanOncology Trials)

Rio Piedras, Puerto Rico, 00935, Puerto Rico

Location

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Pancreatic Neoplasms; Colonic Neoplasms; Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Alberto Bessudo, MD

  California Cancer Associates for Research and Excellence, Inc. (cCare)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 3+3 Dose Escalation Design with Expansion

Study Record Dates

• First Submitted: August 1, 2022
• First Posted: August 3, 2022
• Study Start: August 1, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: September 24, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

PR (1); US (13)