Preliminary Safety Data
Patients treated with OKI-219 at three dose levels (300 mg BID, 600 mg BID, and 900 mg BID) have shown the drug to be generally well tolerated. A total of 17 patients, including those with HR+/HER2- breast cancer, HER2+ breast cancer, colorectal cancer, triple negative breast cancer, and squamous cell carcinoma, have been dosed. No dose-limiting toxicities, dose interruptions, or dose reductions were required. The most common treatment-related adverse events (TRAEs) were Grade 1 diarrhea (N=4), Grade 1 nausea (N=2), and Grade 1 pruritus (N=2).
Pharmacokinetic and Selectivity Profile
OKI-219 has demonstrated favorable pharmacokinetic (PK) data, supporting pharmacologically relevant exposures even at the lowest assessed dose levels. The safety profile suggests minimal or no inhibition of wild-type PI3Kα. At steady state, exposures of OKI-219 exceed those associated with robust antitumor activity in preclinical models.
PIKture-01 Trial Overview
PIKture-01 is a global, multi-center, first-in-human phase 1a/1b study evaluating OKI-219 as monotherapy and in combination with fulvestrant or trastuzumab in subjects with advanced solid tumors, including breast cancer harboring a PI3KαH1047R mutation. The study includes a dose optimization phase to evaluate the optimal combination doses of OKI-219 with fulvestrant or trastuzumab.
Pre-Clinical Data
Preclinical in vivo data indicate that OKI-219, when used in combination with standard-of-care therapies for mutant-selected solid tumors, including breast cancers, exhibits potent anti-tumor activity with excellent tolerability. The drug shows strong combination activity in doublet with SERDs and in triplet with SERD + CDK4/6 inhibitors.
Pipeline Progress
OnKure is actively pursuing additional early-stage discovery programs targeting oncogenic mutations of PI3Kα, aiming to deliver highly selective drug candidates that preserve wild-type PI3Kα while effectively targeting the majority of PI3Kα-mutated cancers. The company expects to announce a pan-mutant development candidate in the first half of 2025 and a development candidate targeting PI3Kα E545K and E542K mutations in 2026.
Conference Call
OnKure will host a conference call and live webcast to discuss the preliminary data from the PIKture-01 trial of OKI-219, which will be presented at SABCS. Details for participation and access to the webcast are provided.
About OnKure
OnKure is a clinical-stage biopharmaceutical company focused on the discovery and development of precision medicines targeting biologically validated drivers of cancers underserved by available therapies. The company is developing OKI-219, a selective PI3KαH1047R inhibitor, as its lead program.
