Cancer, Cancer of Pancreas, Colon Cancer, Colorectal Cancer, Lung Cancer, Non Small Cell Lung Cancer, Solid Tumor
Conditions
Keywords
KRAS G12C, FIH
Brief summary
A Phase 1 dose escalation study in patients with advanced solid tumors harboring KRAS G12C mutation to determine the maximum tolerated dose and recommended Phase II dose of HBI-2438 and characterize its pharmacokinetic profile.
Detailed description
A Phase 1, Open-Label, Dose Escalation of HBI-2438 in Patients with Advanced Malignant Solid Tumors Harboring KRAS G12C Mutation. The primary and secondary objectives are: 1. To determine the MTD and recommended Phase 2 dose (RP2D) of HBI-2438 as an oral monotherapy for advanced solid tumors harboring KRAS G12C mutation. 2. To characterize the PK of HBI-2438 in subjects with advanced malignant solid tumors harboring KRAS G12C mutation. HBI-2438 is an orally administered KRAS G12C Inhibitor and will be dosed once daily throughout the escalation and expansion phase. Up to 44 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 150 to 1200mg. Once the MTD of RP2D is established, an additional 6-8 subjects with brain metastases will be enrolled into the expansion phase at that dose level.
Interventions
DRUGHBI-2438
KRAS G12C 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 G12C mutation- as determined by genetic testing Must have failed or refused standard of care therapy, are not eligible for standard of care therapy, or cannot benefit from standard of care therapy, in the opinion of the Investigator 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 Expected survival time \> 3 months in the opinion of the investigator Must be able to swallow oral medications and must not have gastrointestinal abnormalities that significantly affect drug absorption
Exclusion criteria
Key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| adverse events (AEs), and serious adverse events (SAEs) overall | Up to 36 months | Safety endpoints: adverse events (AEs), and serious adverse events (SAEs) overall |
| To determine the maximum tolerated dose (MTD) | Up to 36 months | Safety endpoints: Incidence of dose-limiting toxicities (DLTs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC) | Cycle 1 (21 days) | Pharmacokinetic variables including Area Under the Curve (AUC) |
| Pharmacokinetic variables including clearance | Cycle 1 (21 days) | Pharmacokinetic variables including clearance |
| minimum plasma concentration (Cmin) | Cycle 1 (21 days) | Pharmacokinetic variables including minimum plasma concentration (Cmin) |
| Pharmacokinetic variables including volume of distribution | Cycle 1 (21 days) | Pharmacokinetic variables including volume of distribution |
| Pharmacokinetic variables including serum half-life | Cycle 1 (21 days) | Pharmacokinetic variables including serum half-life |
| maximum plasma concentration (Cmax) | Cycle 1 (21 days) | Pharmacokinetic variables including maximum plasma concentration (Cmax) |
Countries
Puerto Rico, United States
Outcome results
None listed