Racura Oncology has dosed the first patient in the Phase Ia/b HARNESS-1 trial assessing RC220 in combination with osimertinib for epidermal growth factor receptor-mutant non-small cell lung cancer (EGFR-mutant NSCLC).

The patient received RC220 at 50mg/m² intravenously and did not report any adverse events.

The trial is designed to determine if RC220, a proprietary formulation of (E,E)-bisantrene, can be safely used with osimertinib to help delay or prevent resistance to EGFR tyrosine kinase inhibitors (TKIs), which remain a challenge in this patient population.

EGFR-mutant NSCLC represents a molecularly defined subtype often facing acquired resistance to therapies such as osimertinib.

Mechanisms underlying resistance include secondary EGFR mutations, bypass receptor activation, reactivation of cell signalling pathways, and tumour adaptation processes.

RC220 targets non-canonical G-quadruplex deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) structures in regulatory regions critical for cancer proliferation, aiming to disrupt key oncogenic pathways such as cellular myelocytomatosis oncogene (c-MYC).

The multi-centre trial is structured to assess the biomarkers, molecular response, pharmacodynamics, pharmacokinetics, safety, and tolerability.

It includes an observational screening stage utilising circulating tumour DNA (ctDNA) to confirm patient eligibility.

The Phase Ia dose-escalation stage initially involves single-patient cohorts at increasing doses, progressing to establish the maximum tolerated dose for broader evaluation in up to 40 patients.

A double-blind, randomised Phase Ib expansion stage will then monitor safety, pharmacokinetics and early clinical activity, including survival outcomes and molecular response.

The first patient was treated at Monash Health in Clayton, Victoria, Australia, with other trial sites planned in the near future.

Racura Oncology CEO Daniel Tillett said: “Dosing the first patient in HARNESS-1 is an important milestone for Racura and for the clinical development of RC220. The scientific rationale for this trial is grounded in the urgent need to address TKI therapeutic resistance in EGFR-mutant NSCLC."