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

NCT05163028 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HBI-2376-101
• Study Type: interventional
• Target: 42
• Locations: 2 countries
• Sites: 12

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.

Conditions

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

Keywords

KRAS; EGFR; SHP2; FIH

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Pharmacokinetic variables including maximum plasma concentration (Cmax)

  Cycle 1 (28 days)

• Pharmacokinetic variables including minimum plasma concentration (Cmin)

  Cycle 1 (28 days)

• Pharmacokinetic variables including Area Under the Curve (AUC)

  Cycle 1 (28 days)

• Pharmacokinetic variables including clearance

  Cycle 1 (28 days)

• Pharmacokinetic variables including serum half-life

  Cycle 1 (28 days)

Study Arms (1)

Dose Escalation and Expansion

EXPERIMENTAL

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

Interventions

HBI-2376 DRUG

SHP2 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 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

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
• 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

Sponsors & Collaborators

• HUYABIO International, LLC.: lead

Study Sites (12)

City of Hope

Duarte, California, 91010, United States

Location

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

Encinitas, California, 92024, United States

Location

Providence Medical Foundation

Fullerton, California, 92835, United States

Location

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

San Marcos, California, 92069, United States

Location

Sarcoma Oncology

Santa Monica, California, 90403, United States

Location

UCLA Hematology/Oncology

Santa Monica, California, 90404, United States

Location

Orlando Health, Inc.

Orlando, Florida, 32806, United States

Location

BRCR Medical Center

Plantation, Florida, 33322, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Texas Oncology - Tyler

Tyler, Texas, 75702, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Pan American Center for Oncology Trials (PanOncology Trials)

Rio Piedras, Puerto Rico, 00935, Puerto Rico

Location

MeSH Terms

Conditions

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

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; 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

• Ravi Salgia, MD

  City of Hope Comprehensive Cancer Center

  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: November 24, 2021
• First Posted: December 20, 2021
• Study Start: December 13, 2021
• 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 (11)