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

Sponsor

HUYABIO International, LLC. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05163028

Collaborator

(none)

Enrollment

Locations

Arm

35.6

Anticipated Duration (Months)

3.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer Colorectal Cancer Pancreatic Cancer Solid Tumor Cancer Cancer of Pancreas Cancer of Colon	Drug: HBI-2376	Phase 1

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:

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
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 Design

Study Type:

Interventional

Anticipated Enrollment :

42 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Intervention Model Description:

3+3 Dose Escalation Design with Expansion3+3 Dose Escalation Design with Expansion

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 13, 2021

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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. [Up to 36 months]
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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	California Cancer Associates for Research and Excellence, Inc. (cCare)	Encinitas	California	United States	92024
3	Providence Medical Foundation	Fullerton	California	United States	92835
4	California Cancer Associates for Research and Excellence, Inc. (cCare)	San Marcos	California	United States	92069
5	Sarcoma Oncology	Santa Monica	California	United States	90403
6	UCLA Hematology/Oncology	Santa Monica	California	United States	90404
7	Orlando Health, Inc.	Orlando	Florida	United States	32806
8	BRCR Medical Center	Plantation	Florida	United States	33322
9	Gabrail Cancer Center	Canton	Ohio	United States	44718
10	Texas Oncology - Tyler	Tyler	Texas	United States	75702
11	Virginia Cancer Specialists	Fairfax	Virginia	United States	22031
12	Pan American Center for Oncology Trials (PanOncology Trials)	Rio Piedras		Puerto Rico	00935