Background
Immunotherapy has significantly improved survival in patients with metastatic melanoma, achieving objective response rates of 45-60% and long-term survival However, outcomes remain suboptimal for many patients, and further improvement is needed. Preclinical and early clinical data suggest synergistic effects between stereotactic body radiotherapy (SBRT) and checkpoint inhibitor with an acceptable safety profile.
Methods
AXIOM is a phase II, multicentre, randomised trial designed to evaluate the effectiveness and safety of upfront SBRT to all radiologically identified metastasis with immunotherapy over historical immunotherapy alone (standard of care) in patients with 1-5 extracranial melanoma oligometastases (ClinicalTrials.gov: NCT06767306). The sample size calculation is based on a single-arm design along with a contemporary control arm to confirm historical data, without a formal comparison between the two arms. The study is powered at 80% to detect a 15% absolute improvement in OS rate at the 3-year landmark in the interventional arm. A total of 129 patients will be randomised in a 2:1 ratio to receive either SBRT combined with immunotherapy (n=86) or immunotherapy (n=43). SBRT delivers minimum biologically effective dose of 48Gy₁₀ to all lesions between cycles 1-3 of immunotherapy. Immunotherapy options include anti-PD-1 monotherapy or combination with anti-CTLA-4 or anti-LAG-3 agents.
The primary endpoint is overall survival. Secondary endpoints include progression-free survival, overall response rate, local control, safety, and quality of life outcomes. Correlative translational studies will explore predictive and prognostic biomarkers associated with response, resistance or toxicity.
The trial is currently recruiting at 5 sites in Australia and Canada.
Conclusion
AXIOM will evaluate whether the addition of upfront SBRT to immunotherapy improves outcomes in patients with oligometastatic melanoma. The results will inform the design of future phase III trials and may identify patient subgroups most likely to benefit from combined local and systemic therapy.