A Dose Escalation Study Of SHP2 Inhibitor In Patients With Solid Tumors Harboring KRAS Of EGFR Mutations

Study Overview

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

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.

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

DRUG: HBI-2376

HBI-2376-101

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2021-11-24	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2023-09-12
First Submitted that Met QC Criteria 2021-12-06	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2023-09-13
First Posted (ACTUAL) 2021-12-20	Results First Posted N/A	Last Verified 2023-09

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Sequential

Masking:
None

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

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

Primary Outcome Measures	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	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 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)
Pharmacokinetic variables including volume of distribution	Pharmacokinetic variables including volume of distribution	Cycle 1 (28 days)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: John Ning, MD,PhD,FAIC

Phone Number: 858-280-1866

Email: jning@huyabio.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Ravi Salgia, MD, City of Hope Comprehensive Cancer Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Clinical Trial Record