Clinical trial NCT05485974: A Dose Escalation Study of HBI-2438 in Patients With Solid Tumors Harboring KRAS G12C Mutation
Official title: A Phase 1, Open Label, Dose Escalation of HBI-2438 in Patients With Advanced Malignant Solid Tumors Harboring KRAS G12C Mutation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Lung Cancer
Non Small Cell Lung Cancer
Colorectal Cancer
Cancer of Pancreas
Colon Cancer
Solid Tumor
Cancer
Keywords: KRAS G12C
FIH
Lead sponsor: HUYABIO International, LLC.
Sponsor class: INDUSTRY
First posted: 2022-08-03
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: 3+3 Dose Escalation Design with Expansion
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: To determine the maximum tolerated dose (MTD)
timeFrame: Up to 36 months
measure: adverse events (AEs), and serious adverse events (SAEs) overall
timeFrame: Up to 36 months
Secondary outcomes:
measure: maximum plasma concentration (Cmax)
timeFrame: Cycle 1 (21 days)
measure: minimum plasma concentration (Cmin)
timeFrame: Cycle 1 (21 days)
measure: Area Under the Curve (AUC)
timeFrame: Cycle 1 (21 days)
measure: Pharmacokinetic variables including clearance
timeFrame: Cycle 1 (21 days)
measure: Pharmacokinetic variables including serum half-life
timeFrame: Cycle 1 (21 days)
measure: Pharmacokinetic variables including volume of distribution
timeFrame: Cycle 1 (21 days)
Other outcomes:
Locations:
city: Encinitas
country: United States
facility: California Cancer Associates for Research and Excellence, Inc. (cCare)
state: California
city: Glendale
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Long Beach
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Pasadena
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: San Marcos
country: United States
facility: California Cancer Associates for Research and Excellence, Inc. (cCare)
state: California
city: Santa Ana
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology
state: California
city: Whittier
country: United States
facility: Innovative Clinical Research Institute (ICRI)
state: California
city: Whittier
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Plantation
country: United States
facility: BRCR Medical Center
state: Florida
city: Farmington Hills
country: United States
facility: Michigan Center of Medical Research
state: Michigan
city: Kansas City
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Missouri
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Rio Piedras
country: Puerto Rico
facility: Pan American Center for Oncology Trials (PanOncology Trials)
Study officials:
affiliation: California Cancer Associates for Research and Excellence, Inc. (cCare)
name: Alberto Bessudo, MD
role: PRINCIPAL_INVESTIGATOR
References: