ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12626000325303

Ethics application status

Approved

Date submitted

24/01/2026

Date registered

13/03/2026

Date last updated

3/06/2026

Date data sharing statement initially provided

13/03/2026

Type of registration

Prospectively registered

Titles & IDs

Public title

A Study of the Safety, Pharmacokinetics and Exploratory Efficacy of
RC220 in Combination with Osimertinib in Adult Patients with Non-
Small Cell Lung Cancer.

Scientific title

A Phase 1 Dose Escalation and Expansion Study to Investigate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Intravenous RC220 in Combination with Osimertinib in Patients with EGFR-mutant Non-Small Cell Lung Cancer

Additional trial identifiers [1]

RAC-020

Universal Trial Number (UTN)

Trial acronym

HARNESS-1

Related trial records

Health condition

Health condition(s) studied:

Non-Small Cell Lung Cancer (NSCLC) with activating Epidermal Growth Factor Receptor (EGFR) mutations

Condition category

Condition code

Cancer

Lung - Non small cell

Intervention/exposure

Study type

Interventional

Description of the intervention or exposure

This study has two parts: Part 1 (molecular pre-screening) and Part 2: dose escalation.

Part 1: Participants will be those diagnosed with NSCLC with an activating EGFRm and on a stable maintenance dose of standard of care (SOC) medication, daily oral osimertinib (80 mg), for at least 6 months prior to study enrolment. No interventional treatment is administered. Participants will be required to provide blood samples for evaluation of levels of their activating mutated EGFR ctDNA and will continue to be monitored by standard of care imaging for their disease status. Visits for blood sampling, vital signs, adverse events and concomitant medication assessments will occur onsite (outpatient) or at home via a study nurse. If there is evidence of disease progression then participants will be invited to proceed to screening for enrolment into Part 2 for treatment with study drugs. Monitoring of participants in Part 1 will continue until sufficient participants have been recruited to the interventional (treatment) phase of the study or until study termination. This is expected to be up to 2 years from the start of the study.

Part 2 (Dose Escalation) will comprise sequential, open-label, dose escalation cohorts to determine the maximum tolerated dose (MTD). Participants will receive daily oral fixed dose standard of care osimertinib (80 mg), in combination with up to 7 escalating single doses of RC220. RC220 will be administered intravenously as a 1-hour infusion on Day 1 of each 21-day cycle.

Planned RC220 doses:
Dose level 1 (starting dose) - 50 mg/m2
Dose level 2 - 100 mg/m2
Dose level 3 - 150 mg/m2
Dose level 4 - 200 mg/m2
Dose level 5 - 250 mg/m2
Dose level 6 - 300 mg/m2
Dose level 7 - 350 mg/m2

Treatment (RC220 plus osimertinib) will continue for up to 1 year from the first RC220 dose (approximately 12 months from Cycle 1 Day 1).

Adherence to study drugs RC220 and the standard of care osimertanib will be monitored through study drug accountability records, infusion administration records for IV RC220 and tablet counts of returned medication for oral osimertanib at each scheduled visit.

Intervention code [1]

Treatment: Drugs

Description of the comparator or control

No control group.

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Part 2. Safety and tolerability of RC220 in combination osimertinib. This will be assessed as a composite outcome.

Timepoint [1]

Safety and tolerability evaluations will be made from first dose through 30 days after the final dose of study treatment. Laboratory assessments and vital signs will be conducted at Screening, on Day 1 of each 21-day cycle, and at the end-of-treatment and end-of-study visits. A full physical examination will be performed at Screening. Partial (symptom-directed) physical examinations will be performed on Day 1 of each 21-day cycle, and at the end-of-treatment and end-of-study visits. ECGs will be performed at Screening, on Days 1, 2 and 3 of Cycle 1, on Day 1 of Cycle 2, and at the end-of-treatment and end-of-study visits.

Primary outcome [2]

Part 2: Incidence of dose-limiting toxicities (DLTs). This will be assessed as a composite outcome.

Timepoint [2]

During first 21 days of combination treatment.

Primary outcome [3]

Part 2. To identify the maximum tolerated dose (MTD). This will be assessed as a composite outcome.

Timepoint [3]

From Cycle 1 Day 1 to 30 day safety follow up visit.

Secondary outcome [1]

Part 2: Time to treatment failure (TTF)

Timepoint [1]

Cycle 1 day 1 to 12 months

Secondary outcome [2]

Part 2. Overall Survival (OS)

Timepoint [2]

Time from first dose of RC220 and osimertinib to death or date of censoring. Participants alive or those lost to follow-up will be censored at the last date known to be alive.

Secondary outcome [3]

Part 2: Best Overall Response (BOR) where BOR is defined as the proportion of participants with radiographic confirmed, Investigator-assessed, best overall response of complete response (CR), partial response (PR) or stable disease (SD)

Timepoint [3]

At 6 months from first dose of RC220 in combination with osimertinib,

Secondary outcome [4]

Part 2: Objective response rate (ORR) defined as the proportion of participants who achieve radiographic confirmed, Investigator-assessed, complete response (CR) or partial response (PR)

Timepoint [4]

From baseline until disease progression or end of study (up to 12 months from first dose).

Secondary outcome [5]

Part 2: Progression-free survival (PFS)

Timepoint [5]

Time from the date of the first dose of RC220 and osimertinib to the date of the first documentation of disease progression (radiographic confirmed, Investigator-assessed), or death due to any cause (assessed using medical records), whichever occurs first.

Secondary outcome [6]

Part 2: Pharmacokinetics (PK) of RC220 in plasma and levels of osimertinib and any relevant metabolite(s)

Timepoint [6]

RC220: Cycle 1 (pre-dose, then post-start of infusion: 65 min, 75 min, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 24 hr, 48 hr) Osimertinib: Cycle 1 (pre-dose, then 4 hr, 24 hr and 48 hours) RC220 and osimertinib: Cycle 2 (pre-dose, then 4 hrs post dose) Cycle 3 (pre-dose, then 4 hrs post dose) Cycle 4 (pre-dose, then 4 hrs post dose)

Eligibility

Key inclusion criteria

Inclusion Criteria for Part 1 (Molecular Pre-Screening):
1. Participant has provided consent.
2. 18 years to 80 years of age on the day of consent.
3. Life expectancy greater than or equal to 6 months according to Investigator’s best judgement.
4. ECOG performance status 0 or 1.
5. Diagnosis of confirmed NSCLC with an activating EGFRm known to confer sensitivity to EGFR TKIs.
6. Receiving stable maintenance dose of osimertinib (80 mg daily) for at least 6 months prior to enrolment.
7. No evidence of radiological progression of disease (by computed tomography [CT] scan performed within 6 weeks prior to study enrolment) based on RECIST v1.1
8. Peripheral venous access or access via central venous catheter or implantable port system is sufficient and suitable for repeated venipuncture

Inclusion Criteria for Part 2 (Dose Escalation):
1. Participant (or legally authorised representative) has voluntarily agreed to study participation by giving written informed consent.
2. Participant must be 18 years to 80 years.
3. Life expectancy greater than or equal to 3 months.
4. ECOG performance status 0 or 1.
5. Diagnosis of confirmed NSCLC with an activating EGFR mutation known to confer sensitivity to EGFR TKIs.
6. Receiving stable maintenance dose of osimertinib (80 mg daily) for at least 6 months prior to enrolment.
7. Any of the following during the Part 1 molecular pre-screening phase:
a. Radiological (by CT) progressive, measurable or evaluable disease by RECIST v1.1; or
b. a positive activating EGFRm ctDNA result.
8. Adequate haematological, liver, and kidney function as follows:
a. Bone marrow reserve:
i. Absolute neutrophil count greater than or equal to 1.5 × 10^9/L without growth factor support in the 2 weeks prior to study entry.
ii. Haemoglobin greater than or equal to 90 g/L without transfusion and/or without growth factor support in 2 weeks prior to study entry.
iii. Platelet count greater than or equal to 100 × 10^9/L without transfusion in 2 weeks prior to study entry.
b. Hepatic function:
i. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) < 3 × upper limit of normal (ULN; less than or equal to 5 × ULN if liver metastases)
ii. Total bilirubin less than or equal to 1.5 x ULN if no liver metastases, or < 3 x ULN in presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases.
c. Renal Function:
i. Serum creatinine less than or equal to 1.5 x ULN or serum creatinine clearance (CrCL) greater than 50 mL/min, as per the Cockcroft-Gault Equation.
9. Adequate cardiac function at screening, as determined by:
a. Systolic blood pressure less than 160 mm Hg and diastolic blood pressure less than 100 mm Hg (Grade less than or equal to 2) including with the use of antihypertensive therapy
b. Left ventricular ejection fraction (LVEF) greater than or equal to 50% by echocardiogram
c. No clinically significant ECG waveform abnormalities.
d. QTcF less than or equal to 470 msec, as determined by the mean QTcF values from the ECG assessments at screening (one triplicate)
10. International normalised ratio (INR) /prothrombin time < 2 x ULN, activated partial thromboplastin time (aPTT) less than or equal to 1.5 xULN.
11. Female participants must not be pregnant or lactating, and must be
a. Surgically sterile, or
b. Use highly effective contraceptive method or intrauterine hormone-releasing system used for at least 4 weeks prior to screening, and condom for male partner from screening until at least 30 days after the last administration of study drug, or
c. Post-menopausal for greater than or equal to 12 months, or
d. Female participants who are abstinent from heterosexual intercourse as part of their usual lifestyle will also be eligible for participation.
12. Women of childbearing potential (WOCBP) must agree to abstain from egg donation through 30 days after the last administration of study drug.
13. Males must be:
a. Surgically sterile (> 90 days since vasectomy with documentation of azoospermia 90 days after procedure) and agree to use a condom from screening at least 90 days after the last administration of study drug, or
b. Abstinent from heterosexual intercourse as part of their usual lifestyle, or
c. If engaged in sexual relations with a WOCBP, the female partner of male participant must either be surgically sterile or,
d. Use an acceptable, highly effective contraceptive method from screening at least 90 days after the last administration of study drug. Acceptable methods of contraception include simultaneous use of condoms and effective contraceptive for the female partner (WOCBP) that includes: OCPs, long-acting implantable hormones, injectable hormones, a vaginal ring or an IUD used for at least 4 weeks prior to screening.
14. Male participants must agree to refrain from donating sperm from screening until at least 90 days after the last administration of study drug.
15. Peripheral venous access or access via central venous catheter or implantable port system is sufficient and suitable for repeated venipuncture

Minimum age

18 Years

Maximum age

80 Years

Sex

Both males and females

Healthy volunteers

Key exclusion criteria

Exclusion Criteria for Part 1 - Molecular Pre-Screening:
1. Participation in a concurrent interventional trial.
2. Persisting Grade 2 or higher severity AEs (except alopecia and neuropathy) from prior antitumour treatment, including as a result of maintenance osimertinib therapy, as per NCI-CTCAE v5.0.

Exclusion Criteria for Part 2 (Dose Escalation):
1. Females who are pregnant or lactating.
2. Participants with bronchial (including atelectasis), mediastinal, pleural or vascular involvement.
3. Have received cancer-directed therapy within the following timeframes:
a. Antitumour therapy (chemotherapy, antibody therapy, molecular targeted therapy, hormonal therapy or investigational agent) within 28 days prior to the first dose of RC220 (or 5 times the half-life if shorter than 28 days), except for osimertinib.
Note: exceptions may be considered on a case-by-case basis, as approved by the Sponsor Medical Monitor (MM) based on pharmacology.
b. Wide-field radiation therapy within 28 days (or palliative radiation therapy within 7 days) prior to the first dose of RC220, or the participant has not recovered from the side effects of radiation therapy in the opinion of the Investigator.
Note: Limited radiation to oligometastatic lesions (up to 3 at a time) is permitted.
c. Any other concurrent investigational device(s), investigational agent(s) or conventional agent(s) within 28 days (unless 5 times the half-life is shorter than 28 days) prior to the first dose of RC220.
d. Therapeutic radiopharmaceuticals must be stopped 8 weeks prior to the first dose of RC220.
4. Persisting Grade 2 or higher severity AEs (except alopecia and neuropathy) from prior antitumour treatment, including as a result of maintenance osimertinib therapy, as per NCI-CTCAE v5.0.
5. Participants with primary CNS malignancy, symptomatic CNS metastases, meningeal metastases, carcinomatous meningitis or leptomeningeal disease.
Note: Participants with asymptomatic CNS metastases are eligible if clinically controlled.
6. Had major surgery within 28 days of the screening visit. Exception: no waiting period applies following central venous catheter placement.
7. History of tissue or organ transplantation.
8. Treatment with systemic immunosuppressive or myelosuppressive medications within 4 weeks prior to the first dose of RC220 that would, in the opinion of the Investigator, increase the risk of serious neutropenic complications. Exceptions: daily prednisone or
equivalent less than or equal to 10 mg/day; topical, inhaled or intranasal corticosteroids.
9. History of severe infection deemed clinically significant by the Investigator or designee within 4 weeks, or signs and symptoms of any active infection within 2 weeks prior to the first dose of RC220.
10. Active hepatitis B or C. Note: Hepatitis B virus (HBV) carriers without active disease (HBV DNA titre < 1000 copies/mL or 200 IU/mL) or cured hepatitis C (negative HCV RNA test) with confirmed viral clearance that are not receiving ongoing treatment and without residual chronic liver disease may be enrolled.
11. Confirmed human immunodeficiency virus (HIV) infection and receiving anti-retroviral therapy (ART). Participants with well controlled HIV infection (i.e., CD4+ count >350 cells per microlitre and viral copies less than 400/mL after at least 4 weeks of ART) may be eligible per discretion of the Investigator and with approval from Sponsor MM.
12. Participants with any inherited predisposition to bleeding or to thrombosis (von Willebrand disease, haemophilia, etc.). Participants with a history of nontraumatic haemorrhage (i.e., end stage liver disease, any haemorrhage requiring medical intervention), thromboembolic event or any condition which may increase bleeding risk including clotting disorders, thrombocytopenia during the last 3 months prior to the first dose of RC220.
13. Any other disease or clinically significant abnormality in laboratory parameters, including serious medical or psychiatric illness/condition, which in the judgement of the Investigator might compromise the safety of the participant or integrity of the study, interfere with participation in the trial or compromise the trial objectives.
14. Known allergies, hypersensitivity, or intolerance to the study drugs (RC220, osimertinib), or excipients.
15. Any known, documented, or suspected history of illicit substance abuse that would preclude study participation. Exception: Physician-prescribed medicinal opioids or cannabinoids are allowed for pain management, at the discretion of the Investigator and
in consultation with the Sponsor MM, as required.
16. Vaccination with any live vaccine within 4 weeks prior to the first dose of study treatment.
17. Use of new prescription or non-prescription medications, including complementary medicines, if the medication is a potential inhibitor of cytochrome P450 (CYP) isoform 3A4 and/or P-glycoprotein (P-gp), or if the medication is an inducer of CYP3A4 or P-gp,
throughout study participation.
18. Severe or uncontrolled cardiac disease requiring treatment, CHF (New York Heart Association) NYHA III or IV, unstable angina pectoris even if medically controlled, history of myocardial infarction during the 6 months prior to screening, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia).
19. History of pneumonitis or interstitial lung disease.
20. Judgement by the Investigator that the participant is unlikely to comply with study procedures, restrictions and requirements.
21. Psychological, familial, sociological, or geographical conditions that are likely to interfere with compliance to the protocol.

Study design

Purpose of the study

Treatment

Allocation to intervention

Non-randomised trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Other design features

Phase

Phase 1

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

1/04/2026

Actual

31/03/2026

Date of last participant enrolment

Anticipated

3/07/2028

Actual

Date of last data collection

Anticipated

2/07/2029

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW,QLD,VIC

Recruitment hospital [1]

Monash Medical Centre - Clayton campus - Clayton

Recruitment postcode(s) [1]

3168 - Clayton

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Racura Oncology Ltd.

Address [1]

Country [1]

Australia

Primary sponsor type

Commercial sector/Industry

Name

Racura Oncology Ltd.

Address

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

St Vincent's Hospital Melbourne Human Research Ethics Committee

Ethics committee address [1]

https://svhm.org.au/home/research/researchers/human-research-ethics-committee

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

01/10/2025

Approval date [1]

21/11/2025

Ethics approval number [1]

Summary

Brief summary

The aim of the study is to evaluate the safety, tolerability, PK and preliminary efficacy of intravenous (IV) administered RC220 in combination with oral osimertinib in patients diagnosed with non-small cell lung cancer (NSCLC) with an activating Epidermal Growth Factor Receptor mutation (EGFRm) known to confer sensitivity to EGFR tyrosine kinase inhibitors (TKIs).
Who is it for?
You may be eligible to join this study if you are aged 18 to 80 years of age, with life expectancy greater than 6 months, ECOG performance status 0 or 1, a diagnosis of confirmed Non–Small Cell Lung Cancer (NSCLC) with an activating EGFR mutation (EGFRm). In addition, you must have been receiving a stable maintenance dose of osimertinib (a medication approved under the brand name Tagrisso®) for at least 6 months prior to enrolment and either measurable or evaluable disease or a positive activating EGFRm ctDNA result.
Study details
There are 2 parts to this study
Part 1. ctDNA (molecular) pre-screening. Participants will have blood tests to assess for ctDNA levels of the activating EGFRm identified at diagnosis as an indicator of disease status.  If there are signs your cancer is progressing during this part, you will be invited to participate in the treatment part (Part 2) of the study.  
Part 2 (dose escalation) will investigate effects of escalating doses of RC220 to determine the maximum tolerated dose (MTD) when administered in combination with osimertinib. There will be up to 7 different doses of RC220 used to determine the MTD dose. Each RC220 dose is administered into the vein (IV) on day 1 of a 21-day treatment cycle with daily oral doses of osimertinib (80 mg). If participants don't experience any specific side effects, they will continue to receive study treatment in 21-day cycles.  A new group of participants will receive treatment at a RC220 higher dose if deemed appropriate following a review of safety from the first cycle of treatment in the prior group of participants.
All participants in Part 2 will be monitored with clinical visits, blood tests, electrocardiogram, echocardiogram (heart tests) and radiology images.  
This research will hopefully help further the development of RC220 when given with osimertinib to improve and or extend treatment for NSCLC patients with activating EGFR mutations.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

A/Prof Surein Arulananda

Address

Monash Health, Level 3 Monash Health Translation Precinct 246 Clayton Road Clayton VIC 3168 Australia

Country

Australia

Phone

+61 03 8572 2392

Fax

[email protected]

Contact person for public queries

Name

Rodney Cusack

Address

Racura Oncology, L36/1 Macquarie Pl, Sydney NSW 2000

Country

Australia

Phone

+61 02 8051 3043

Fax

[email protected]

Contact person for scientific queries

Name

Rodney Cusack

Address

Racura Oncology, L36/1 Macquarie Pl, Sydney NSW 2000

Country

Australia

Phone

+61 02 8051 3043

Fax

[email protected]

Data sharing statement

Will the study consider sharing individual participant data?

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

Trial Review

Documents added manually

Documents added automatically