Announcement • Jun 27
Racura Oncology Doses First Patient in Harness-1 Phase 1A/B Trial of Rc220 in Combination with Osimertinib for Egfr-Mutant Non-Small Cell Lung Cancer
Racura Oncology has dosed the first patient in the HARNESS-1 Phase 1a/b trial of RC220 in combination with osimertinib for EGFR-mutant non-small cell lung cancer. The study will assess safety, pharmacokinetics, ctDNA dynamics and early clinical activity of RC220 as a strategy to address therapeutic TKI resistance. The first patient received RC220 at 50 mg/m2 by intravenous infusion. No adverse events were observed. HARNESS-1 is designed to test whether RC220, Racura's proprietary formulation of (E,E)-bisantrene, can be safely combined with osimertinib (Tagrisso; AstraZeneca), a third-generation EGFR tyrosine kinase inhibitor (TKI) and standard-of-care therapy for EGFR-mutant NSCLC to delay or prevent TKI treatment resistance. Although EGFR TKIs have transformed outcomes for many patients with EGFR-driven lung cancer, acquired treatment resistance remains a central therapeutic challenge. EGFR-mutant NSCLC is a molecularly stratified lung adenocarcinoma subtype driven by constitutive EGFR kinase signaling and initial sensitivity to EGFR inhibition. However, responses to EGFR tyrosine kinase inhibitors, including osimertinib, are typically limited by acquired resistance, arising through heterogeneous mechanisms such as secondary EGFR alterations, bypass receptor tyrosine kinase activation, MAPK/PI3K pathway reactivation, oncogenic fusions, lineage plasticity, epithelial-to-mesenchymal transition and histologic transformation. RC220 is being developed to target the non-canonical G-quadruplex DNA and RNA structures enriched in oncogenic regulatory regions, including promoters, untranslated regions and highly transcribed loci. Stabilization of these structures can disrupt transcriptional and post-transcriptional control networks that sustain malignant proliferation, including silencing the c-MYC-regulated growth and survival pathways. HARNESS-1 is designed to evaluate the safety and tolerability of RC220 with continued osimertinib-mediated EGFR suppression, while generating pharmacokinetic, pharmacodynamic, molecular response and translational biomarker data. HARNESS-1 is a multi-center Phase 1a/b clinical study in patients with EGFR-mutant NSCLC receiving osimertinib. The study includes an observational screening stage using ctDNA to help identify eligible patients and characterize tumor molecular status before treatment. The Phase 1a dose-escalation stage will evaluate RC220 administered by intravenous infusion on Day 1 of each 21-day cycle in combination with standard-of-care maintenance osimertinib. The first three dose levels will use single-patient cohorts at 50 mg/m2, 100 mg/m2 and 150 mg/m2, before progressing to larger cohorts to identify the maximum tolerated dose and an appropriate dose for further study. Between 12 and 40 patients are expected to participate in the dose-escalation stage. Following review of available safety and pharmacokinetic data, the study is expected to advance into a double-blind, randomized Phase 1b expansion stage. In this dose expansion stage, 40 patients will receive one of two RC220 dose levels in combination with osimertinib. Patients will be monitored for safety, pharmacokinetics and early signals of clinical activity, including progression-free survival, overall survival, ctDNA dynamics and changes in cancer-specific mutations. The first patient was treated by Principal Investigator Associate Professor Surein Arulananda and his team at Monash Health in Clayton, Victoria. Additional clinical trial sites are expected to open in the coming months to support patient recruitment and study progress. Further details about HARNESS-1, including open and recruiting sites, are available through the Australian and New Zealand Clinical Trial Registry at www.anzctr.org.au under trial code ACTRN12626000325303. RC220 is a proprietary formulation of (E,E)-bisantrene designed to overcome drug solubility issues that prevent safe peripheral intravenous infusion. (E,E)-bisantrene, is a clinical validated small molecule anticancer agent that primarily functions via G4-DNA and RNA binding, leading to potent transcriptional silencing of the important cancer growth regulator c-MYC.
