Overview
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.
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:
- 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.
- 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.
Eligibility
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 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 prior to first dose of HBI-2438; or the presence of unstable angina or congestive heart failure of New York Heart Association Grade 2 or higher
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 KRAS G12C 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