Cancer, Cancer of Colon, Cancer of Pancreas, Colorectal Cancer, Non Small Cell Lung Cancer, Pancreatic Cancer, Solid Tumor
Conditions
Keywords
KRAS, EGFR, SHP2, FIH
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.
Interventions
DRUGHBI-2376
SHP2 Inhibitor
Sponsors
HUYABIO International, LLC.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
3+3 Dose Escalation Design with Expansion
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 maximum plasma concentration (Cmax) | Cycle 1 (28 days) | Pharmacokinetic variables including maximum plasma concentration (Cmax) |
| 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 clearance | Cycle 1 (28 days) | Pharmacokinetic variables including clearance |
Countries
Puerto Rico, United States
Outcome results
None listed