A Phase 2 interventional study of Stereotactic Body Radiotherapy (extracranial) concurrent with Immunotherapy and Immunotherapy alone in Melanoma Metastatic, sponsored by Melanoma Institute Australia. Recruiting at 5 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-05-07.
Sponsored by Melanoma Institute Australia · Phase 2, Interventional, and Treatment
The purpose of this research is to evaluate the addition of radiotherapy to the standard immunotherapy drugs that are given to patients with advanced or metastatic melanoma that has spread to other parts of the body. Radiotherapy uses x-rays to target and kill melanoma cells and immunotherapy works by activating the body's own immune system to seek out and fight melanoma cells. Both of these treatments are commonly given to patients with advanced melanoma and other cancers. Both treatments are usually given separately but can also be given together. The aim of this research is to find out if giving radiotherapy and immunotherapy together is better than giving immunotherapy alone.
The type of radiotherapy to be used in this project is known as 'stereotactic' body radiotherapy or SBRT (also known as stereotactic body ablative radiotherapy, SABR). SBRT targets the radiation very precisely at the metastatic deposits in the body. This method protects the healthy areas near the melanoma. SBRT works by delivering a high dose of radiation precisely to the areas of melanoma which causes the melanoma cells to break apart and eventually die. SBRT is given in 'fractions' which means the high dose is given in small measures over several days, depending on the number and size of metastases.
One of the promising treatment combinations for metastatic melanoma is the use of radiotherapy with immune checkpoint inhibitors. There have been multiple reports of the synergy between radiation and immunotherapy in preclinical studies and early phase clinical trials. This combination improves response rates compared to immunotherapy alone and without worsening the toxicity associated with each agent alone. Radiation has the potential to convert tumours considered immunologically "cold" into "warm" through the combination of three processes: 1) Changes in the balance of cytokines by increasing the production of immunostimulatory cytokines which overcome the immunosuppressive tumour microenvironment, 2) Recruitment, of antigen-presenting cells and immune effector cells in the tumour microenvironment, 3) Positive regulation of antigen expression, antigen processing, histocompatibility molecules, and costimulatory signals, thereby increasing tumour immunogenicity.
There is a significant body of data to suggest a reproducible clinical benefit can be achieved when stereotactic body radiotherapy (SBRT) is used with immunotherapy in a tightly sequenced treatment combination, in contrast to independently timed use of either treatment alone, for the management of a variety of malignancies. In metastatic non-small cell lung cancer, a pooled analysis of two randomised trials showed that the addition of radiotherapy improved the out-of-field response rate, progression-free survival, and the overall survival. In the Stereotactic Ablative Radiotherapy for Comprehensive Treatment of Oligometastatic Tumors trial (SABR-COMET - NCT01446744) of 1-5 oligo metastases in all tumour histologies, the 8-year overall survival was 27.2% in the experimental SBRT arm versus 13.6% in the palliative radiotherapy control arm (with the goal of alleviating symptoms) (hazard ratio, 0.50; 95% confidence interval, 0.30-0.84; P = 0.008). The eight-year progression free survival estimates were 21.3% versus 0.0%, respectively (hazard ratio, 0.45; 95% confidence interval, 0.28-0.72; P \<0.001) (Harrow, Palma et al. 2022). There are two ongoing phase 3 randomised trials of SABR with standard of care (palliative radiotherapy with or without systemic anti-cancer therapy) vs standard of care alone for patients with 1-3 solid cancer metastases (SABR-COMET 3) and 4-10 metastases (SABR- COMET 10).
At present, patients with metastatic melanoma receive various treatment modalities in different combinations and sequencing, including a drug alone approach, palliative radiotherapy for symptom control, SBRT to persistent disease as salvage therapy if all or some metastases do not respond to initial drug therapy, and surgery. There is an ongoing randomised trial examining the role of upfront stereotactic radiosurgery to asymptomatic melanoma brain metastases in patients receiving concurrent combination of ipilimumab and nivolumab (Clinical Trials.gov Identifier: NCT03340129). However, there is no prospective randomised trial on the role of SBRT with immunotherapy in patients with extracranial melanoma oligometastases.
The AXIOM trial seeks to determine the role of upfront SBRT in patients with 1-5 extracranial melanoma oligometastases treated with concurrent immunotherapy. The efficacy of immunotherapy in this patient population is well established and therefore this randomised controlled study design is non-comparable with the control group. The randomisation ratio of 2:1 will provide more information on the response and safety of SBRT and immunotherapy, whilst limiting the number of patients randomised to the 'control' group, in order to provide minimum but contemporary immunotherapy efficacy and safety data.
The hypothesis is that for patients with extracranial melanoma oligometastases, concurrent stereotactic body radiotherapy with immunotherapy is safe and prolongs survival through enhanced anti-tumour immunity due to the potential synergy of the combination therapies, than immunotherapy alone.
Melanoma Institute Australia is the lead sponsor of 16 studies on the registry; 7 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Concurrent stereotactic body radiotherapy (SBRT) with standard of care immune checkpoint inhibitor(s) (ICI). Patients will receive a minimum SBRT biologically effective dose (BED) of 48Gy10 to all sites of metastatic disease between cycle 1 and cycle 3 of immunotherapy. The interval between cycles 1 and 3 will depend on the prescribed immunotherapy regimen that is standard of care at each participating site. Standard of care 1st line immunotherapy, as decided by the treating clinician and in accordance with the current listing on the Australian Register of Therapeutic Goods (ARTG) or applicable international regulatory agency will be administered concurrently
Immunotherapy alone Standard of care 1st line immunotherapy, as decided by the treating clinician and in accordance with the current listing on the Australian Register of Therapeutic Goods (ARTG) or applicable international regulatory agency will be administered alone.
Drug: Immunotherapy alone
Radiotherapy A minimum SBRT biologically effective dose (BED) of 48Gy10 to all sites of extracranial metastatic disease should be administered between cycle 1 and cycle 3 of standard of care immunotherapy. Immunotherapy All patients will receive standard of care 1st line immunotherapy as decided by the treating clinician and in accordance with the current listing on the Australian Register of Therapeutic Goods (ARTG) or applicable international regulatory agency. Other Names: Immune checkpoint inhibitor Standard of care immunotherapy First line treatment
All patients will receive standard of care 1st line immunotherapy as decided by the treating clinician and in accordance with the current listing on the Australian Register of Therapeutic Goods (ARTG) or applicable international regulatory agency.
Also known as: Immune checkpoint inhibitor, Standard of care immunotherapy, First line treatment
Overall survival
Proportion of patients alive at 6 months 1, 2, 3 and 5 years from the time of randomization
Time frame: 5 years
Overall progression-free survival
Proportion of patients alive and with no evidence of disease progression or new melanoma lesions as assessed by RECIST 1.1 criteria
Time frame: 5 years
Progression-free survival related to new lesions only
Proportion of patients alive and with no evidence of new melanoma lesions as assessed by RECIST 1.1 criteria
Time frame: 5 years
Overall response rate
Overall response rate from the time of randomization to the best response as assessed by RECIST 1.1
Time frame: 5 years
Local control of the initial oligometastases
The proportion of patients with local control of all baseline metastases: complete response, partial response or stable disease) as assessed per RECIST 1.1 criteria
Time frame: 5 years
Safety and tolerability of each treatment arm and study procedures
Proportion of patients with adverse events related to SBRT alone, combined SBRT and immunotherapy, immunotherapy-related Suspected Unexpected Serious Adverse Reaction (SUSAR), or related to study specific procedures with causality determined by the investigator and described per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Only AEs greater than CTCAE grade 1 will be recorded.
Time frame: 5 years
The requirement for immunosuppressive agents to treat adverse events
Proportion of patients receiving corticosteroids or other immunosuppressive agents to treat each adverse event including duration and maximum dose.
Time frame: 5 years
Patient reported quality of life
The mean change from baseline quality of life scores \[EuroQol Group Association ED-5Q-5L and European Organisation for Research and Treatment of Cancer QLQ-C30\] from randomization to best and lowest scores for each instrument.
Time frame: 5 years
Salvage radiotherapy in the immunotherapy alone arm
The incidence of salvage radiotherapy for symptomatic control or progressing baseline lesions or new metastasis(es) in the immunotherapy arm.
Time frame: 5 years
Plan to share: Undecided
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Melanoma Institute Australia