A Dose Escalation Study of SHP2 Inhibitor in Patients With Solid Tumors Harboring KRAS of EGFR Mutations

Brief summary public domain (ClinicalTrials.gov)

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 public domain (ClinicalTrials.gov)

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.

Intervention public domain (ClinicalTrials.gov)

Drug: HBI-2376. SHP2 Inhibitor

Arm public domain (ClinicalTrials.gov)

Dose Escalation and Expansion (experimental): HBI-2376 will be given orally in ascending doses (escalation cohort), until the maximum tolerated dose or recommended Phase 2 dose is reached. Up to 6 patients will then be enrolled in the expansion cohort at the recommended dose.

Primary outcome public domain (ClinicalTrials.gov)

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.. 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 Time frame: Up to 36 months.

Secondary outcome public domain (ClinicalTrials.gov)

Pharmacokinetic variables including maximum plasma concentration (Cmax). Time frame: Cycle 1 (28 days).

Secondary outcome public domain (ClinicalTrials.gov)

Pharmacokinetic variables including minimum plasma concentration (Cmin). Time frame: Cycle 1 (28 days).

Secondary outcome public domain (ClinicalTrials.gov)

Pharmacokinetic variables including Area Under the Curve (AUC). Time frame: Cycle 1 (28 days).

Secondary outcome public domain (ClinicalTrials.gov)

Pharmacokinetic variables including clearance. Time frame: Cycle 1 (28 days).

Secondary outcome public domain (ClinicalTrials.gov)

Pharmacokinetic variables including serum half-life. Time frame: Cycle 1 (28 days).

Secondary outcome public domain (ClinicalTrials.gov)

Pharmacokinetic variables including volume of distribution. Time frame: Cycle 1 (28 days).

Eligibility public domain (ClinicalTrials.gov)

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

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 42 participants (estimated).