A Dose Escalation Study of SHP2 Inhibitor in Patients With Solid Tumors Harboring KRAS of EGFR Mutations

A Phase 1, Open-Label, Dose Escalation of HBI-2376 in Patients With Advanced Malignant Solid Tumors Harboring KRAS or EGFR Mutations

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Cancer; Colorectal Cancer; Pancreatic Cancer; Solid Tumor; Non Small Cell Lung Cancer; Cancer of Pancreas; Cancer of Colon
• Intervention / Treatment: Drug: HBI-2376

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:

1. 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
2. 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.

• Study Type: Interventional
• Enrollment (Estimated): 42
• 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
    • Duarte, California, United States, 91010
      • City of Hope
    • Encinitas, California, United States, 92024
      • California Cancer Associates for Research and Excellence, Inc. (cCARE)
    • Fullerton, California, United States, 92835
      • Providence Medical Foundation
    • San Marcos, California, United States, 92069
      • California Cancer Associates for Research and Excellence, Inc. (cCARE)
    • Santa Monica, California, United States, 90404
      • UCLA Hematology/Oncology
    • Santa Monica, California, United States, 90403
      • Sarcoma Oncology
  • Florida
    • Orlando, Florida, United States, 32806
      • Orlando Health, Inc.
    • Plantation, Florida, United States, 33322
      • BRCR Medical Center
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center
  • Texas
    • Tyler, Texas, United States, 75702
      • Texas Oncology - Tyler
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists

Participation Criteria

Eligibility Criteria

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

Description

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

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-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.	Drug: HBI-2376; SHP2 Inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic variables including maximum plasma concentration (Cmax)	Pharmacokinetic variables including maximum plasma concentration (Cmax)	Cycle 1 (28 days)
Pharmacokinetic variables including minimum plasma concentration (Cmin)	Pharmacokinetic variables including minimum plasma concentration (Cmin)	Cycle 1 (28 days)
Pharmacokinetic variables including Area Under the Curve (AUC)	Pharmacokinetic variables including Area Under the Curve (AUC)	Cycle 1 (28 days)
Pharmacokinetic variables including volume of distribution	Pharmacokinetic variables including volume of distribution	Cycle 1 (28 days)
Pharmacokinetic variables including clearance	Pharmacokinetic variables including clearance	Cycle 1 (28 days)
Pharmacokinetic variables including serum half-life	Pharmacokinetic variables including serum half-life	Cycle 1 (28 days)

Collaborators and Investigators

• Sponsor: HUYABIO International, LLC.
• Investigators: Principal Investigator: Ravi Salgia, MD, City of Hope Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: November 24, 2021
• First Submitted That Met QC Criteria: December 6, 2021
• First Posted (Actual): December 20, 2021

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: EGFR; SHP2; KRAS; 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; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplasms; Colorectal Neoplasms; Colonic Neoplasms; Pancreatic Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: HBI-2376-101

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