Clinical trial NCT05163028: A Dose Escalation Study of SHP2 Inhibitor in Patients With Solid Tumors Harboring KRAS of EGFR Mutations
Official title: A Phase 1, Open-Label, Dose Escalation of HBI-2376 in Patients With Advanced Malignant Solid Tumors Harboring KRAS or EGFR Mutations
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Non Small Cell Lung Cancer
Colorectal Cancer
Pancreatic Cancer
Solid Tumor
Cancer
Cancer of Pancreas
Cancer of Colon
Keywords: KRAS
EGFR
SHP2
FIH
Lead sponsor: HUYABIO International, LLC.
Sponsor class: INDUSTRY
First posted: 2021-12-20
Enrollment: 42
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 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.

Eligibility 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

Primary outcomes:
measure: 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.
timeFrame: Up to 36 months
Secondary outcomes:
measure: Pharmacokinetic variables including maximum plasma concentration (Cmax)
timeFrame: Cycle 1 (28 days)
measure: Pharmacokinetic variables including minimum plasma concentration (Cmin)
timeFrame: Cycle 1 (28 days)
measure: Pharmacokinetic variables including Area Under the Curve (AUC)
timeFrame: Cycle 1 (28 days)
measure: Pharmacokinetic variables including clearance
timeFrame: Cycle 1 (28 days)
measure: Pharmacokinetic variables including serum half-life
timeFrame: Cycle 1 (28 days)
measure: Pharmacokinetic variables including volume of distribution
timeFrame: Cycle 1 (28 days)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Encinitas
country: United States
facility: California Cancer Associates for Research and Excellence, Inc. (cCare)
state: California
city: Fullerton
country: United States
facility: Providence Medical Foundation
state: California
city: San Marcos
country: United States
facility: California Cancer Associates for Research and Excellence, Inc. (cCare)
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology/Oncology
state: California
city: Orlando
country: United States
facility: Orlando Health, Inc.
state: Florida
city: Plantation
country: United States
facility: BRCR Medical Center
state: Florida
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Tyler
country: United States
facility: Texas Oncology - Tyler
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Rio Piedras
country: Puerto Rico
facility: Pan American Center for Oncology Trials (PanOncology Trials)
Study officials:
affiliation: City of Hope Comprehensive Cancer Center
name: Ravi Salgia, MD
role: PRINCIPAL_INVESTIGATOR
References: