a dose escalation study of shp2 inhibitor in patients with solid tumors harboring kras of egfr mutations

Conditions: Non Small Cell Lung Cancer; Colorectal Cancer; Pancreatic Cancer; Solid Tumor; Cancer; Cancer of Pancreas; Cancer of Colon

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.

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

Keywords: kras egfr shp2 fih