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

Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05163028
• Other study ID #: HBI-2376-101
• Status: Recruiting
• Phase: Phase 1
• Start date: December 13, 2021
• Est. completion date: December 2024

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 or EGFR mutations to determine the maximum tolerated dose and recommended Phase II dose of HBI-2376 and characterize its pharmacokinetic profile.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• HBI-2376
SHP2 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	City of Hope	Duarte	California
United States	California Cancer Associates for Research and Excellence, Inc. (cCare)	Encinitas	California
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Providence Medical Foundation	Fullerton	California
United States	Orlando Health, Inc.	Orlando	Florida
United States	BRCR Medical Center	Plantation	Florida
United States	California Cancer Associates for Research and Excellence, Inc. (cCare)	San Marcos	California
United States	Sarcoma Oncology	Santa Monica	California
United States	UCLA Hematology/Oncology	Santa Monica	California
United States	Texas Oncology - Tyler	Tyler	Texas

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