On October 12, 2026 Racura Oncology Limited (ASX: RAC), a late clinical-stage biopharmaceutical company developing new small molecule-based approaches to cancer treatment focused on silencing MYC gene expression, reported that the Safety Review Committee (SRC) for HARNESS-1 has cleared its lead oncology drug, RC220 to escalate to the next planned dose level of 100 mg/m2. HARNESS-1 (RAC-020) is a Phase 1a/b clinical trial evaluating RC220 in combination with osimertinib in patients with epidermal growth factor receptor-mutant (EGFR-mutant) non-small cell lung cancer (NSCLC).

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The SRC reviewed all safety data from both Cohort 1 patients, who received RC220 at 50 mg/m2 by intravenous infusion in combination with osimertinib at 80 mg daily. No dose-limiting toxicities or treatment-related safety concerns were identified in either patient during the safety observation period. The second Cohort 1 patient has now received three doses of RC220, administered 21 days apart, without any dose-limiting toxicities or treatment-related safety concerns.

Cohort 1 enrolled two patients after the SRC requested that a second patient receive RC220 at 50 mg/m2. This followed an observation of Grade 2 colitis in the first patient outside the trial safety period. Although the cause was undetermined, a contribution from RC220 could not be excluded. The second patient has reported no colitis or other dose limiting symptoms after three separate RC220 doses.

Pre-screening is now underway to enroll the single patient in Cohort 2, who is expected to receive RC220 at 100 mg/m2 with osimertinib at 80 mg daily. SRC clearance relates to safety and dose escalation only; this announcement does not include data on the clinical activity of RC220 in this indication.

Daniel Tillett, Ph.D., Chief Executive Officer of Racura Oncology, said: "We are pleased with the SRC’s clearance, which allows RC220 to progress to the next dose level in the HARNESS-1 trial. This is an important early milestone for the trial and reflects the disciplined execution of our clinical development plan. The Cohort 1 safety review identified no dose-limiting toxicities or treatment-related safety concerns in either patient during the safety observation period. We thank the patients and their families for supporting this study and acknowledge Principal Investigator, Associate Professor Surein Arulananda and the Monash Health team for their ongoing contribution."

Scientific Rationale

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 (TKIs), including osimertinib (Tagrisso; AstraZeneca), 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 clinically developed to target 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 the silencing of MYC-driven growth and survival pathways.

HARNESS-1 Trial Design

HARNESS-1 is a multicenter Phase 1a/b clinical study in patients with EGFR-mutant NSCLC receiving osimertinib. The study includes an observational screening stage using circulating tumor DNA (ctDNA) to help identify eligible patients and characterize tumor molecular status before treatment.

The Phase 1a dose-escalation stage evaluates RC220 administered by intravenous infusion on Day 1 of each 21-day cycle, in combination with standard-of-care maintenance osimertinib. It uses an accelerated titration design, in which the first three dose levels of 50 mg/m2, 100 mg/m2 and 150 mg/m2 are each evaluated in a single-patient cohort. Each patient is monitored through a 21-day safety observation period, and the SRC reviews all available safety data before the trial moves to the next dose level. This approach allows the trial to move efficiently through lower dose levels that may sit below the expected active range, while limiting patient exposure to higher doses before safety data have been reviewed.

Subject to the protocol and safety outcomes, the trial is expected to transition after the 150 mg/m2 cohort to a Bayesian Optimal Interval (BOIN) design, starting at 200 mg/m2 with at least three patients at each dose level, 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.

Clinical Trial Information

Further details about HARNESS-1, including open and recruiting sites, are available through the Australian New Zealand Clinical Trials Registry at www.anzctr.org.au under trial code ACTRN12626000325303. Clinical trial enquiries may be directed to Racura Oncology at [email protected].

About RC220 & (E,E)-bisantrene

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 clinically 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 MYC and downstream pathways.

(Press release, Racura Oncology, OCT 12, 2026, View Source [SID1234673332])