A Dose Escalation Study of SHP2 Inhibitor in Patients With Solid Tumors Harboring KRAS of EGFR Mutations
- Conditions
- Non Small Cell Lung CancerCancer of PancreasCancer of ColonColorectal CancerPancreatic CancerSolid TumorCancer
- Interventions
- Registration Number
- NCT05163028
- Lead Sponsor
- HUYABIO International, LLC.
- 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.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 42
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation and Expansion HBI-2376 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.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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
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)
Trial Locations
- Locations (11)
Providence Medical Foundation
🇺🇸Fullerton, California, United States
UCLA Hematology/Oncology
🇺🇸Santa Monica, California, United States
BRCR Medical Center
🇺🇸Plantation, Florida, 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)
🇺🇸San Marcos, California, United States
Sarcoma Oncology
🇺🇸Santa Monica, California, United States
Texas Oncology - Tyler
🇺🇸Tyler, Texas, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Pan American Center for Oncology Trials (PanOncology Trials)
🇵🇷Rio Piedras, Puerto Rico
Orlando Health, Inc.
🇺🇸Orlando, Florida, United States