ORIC-114 is a brain penetrant, selective, orally bioavailable, irreversible small molecule inhibitor of EGFR and HER2 alterations, including exon 20 insertion mutations.~This is a first-in-human, open-label, single arm, multicenter, dose escalation followed by dose expansion study to establish the recommended phase 2 dose (RP2D) and preliminary antitumor activity of ORIC-114 in patients with advanced solid tumors harboring an EGFR or HER2 alteration who have exhausted available treatment options~The study will begin with dose finding in patients with various solid tumors (Dose Escalation); additional dose expansion cohorts in specific tumor types (Dose Expansion), treatment history, and/or expression of a specific biomarker may be initiated via protocol amendment.~The study will evaluate escalating dose levels of ORIC-114 administered orally, daily in 28-day cycles following an accelerated titration design used for Dose Level 1, after which, escalating doses of ORIC-114 will be administered following an interval 3+3 design.
The purpose of this study is to establish the recommended Phase 2 dose (RP2D) and/or maximum tolerated dose (MTD), safety, pharmacokinetics (PK), pharmacodynamics (PD), preliminary antitumor ORIC-114 when administered to patients with advanced solid tumors harboring an EGFR or HER2 alteration.