Sydney – October 12, 2026 -- The Safety Review Committee (SRC) for Racura Oncology's HARNESS-1 trial has cleared lead drug RC220 to escalate to 100 mg/m2, after finding no dose-limiting toxicities in either Cohort 1 patient. The Phase 1a/b study combines RC220 with osimertinib in patients with EGFR-mutant non-small cell lung cancer (NSCLC).
Both Cohort 1 patients received RC220 at 50 mg/m2 by intravenous infusion alongside osimertinib at 80 mg daily. The second patient has received three RC220 doses, given 21 days apart, with no dose-limiting toxicities or treatment-related safety concerns.
Racura enrolled a second Cohort 1 patient after a Grade 2 colitis case
Cohort 1 grew to two patients because the SRC asked for a second patient at 50 mg/m2. That request followed Grade 2 colitis in the first patient, observed outside the trial safety period. The cause was undetermined, and a contribution from RC220 could not be excluded. The second patient has reported no colitis or other dose-limiting symptoms.
Pre-screening for the single-patient Cohort 2 is underway
Cohort 2 will enroll one patient to receive RC220 at 100 mg/m2 with osimertinib at 80 mg daily. Racura stated that SRC clearance covers safety and dose escalation only and that the announcement contains no data on clinical activity in this indication.
CEO Daniel Tillett called the clearance an important early milestone that reflects disciplined execution of the clinical development plan.
Accelerated titration covers 50, 100 and 150 mg/m2 in single-patient cohorts
RC220 is given intravenously on Day 1 of each 21-day cycle with standard-of-care maintenance osimertinib. Each patient completes a 21-day safety observation period, and the SRC reviews all available safety data before the next dose level opens.
After the 150 mg/m2 cohort, and subject to protocol and safety outcomes, the trial is expected to move to a Bayesian Optimal Interval (BOIN) design. It would start at 200 mg/m2 with at least three patients per dose level to identify the maximum tolerated dose. Between 12 and 40 patients are expected in the dose-escalation stage.
A 40-patient randomized expansion would follow the escalation stage
Following review of safety and pharmacokinetic data, the study is expected to advance to a double-blind, randomized Phase 1b expansion stage. In it, 40 patients will receive one of two RC220 dose levels combined with osimertinib. Investigators will monitor safety, pharmacokinetics and early signals of clinical activity, including progression-free survival, overall survival, circulating tumor DNA (ctDNA) dynamics and changes in cancer-specific mutations.
The study also includes an observational ctDNA screening stage to help identify eligible patients and characterize tumor molecular status before treatment.
RC220 targets resistance that limits osimertinib responses
Responses to EGFR tyrosine kinase inhibitors, including AstraZeneca's osimertinib (Tagrisso), are typically limited by acquired resistance. RC220 is a formulation of (E,E)-bisantrene designed to overcome solubility issues that prevent safe peripheral intravenous infusion. It targets G-quadruplex DNA and RNA structures, with the aim of silencing MYC-driven growth and survival pathways.
The trial is registered with the Australian New Zealand Clinical Trials Registry under code ACTRN12626000325303. Principal Investigator Associate Professor Surein Arulananda and the Monash Health team are leading the study.