Rare cancers have a unique contribution to Australia’s cancer landscape. As individual cancer types, rare cancers have very low incidences and are defined by 6 or fewer diagnoses for every 100,000 people. And yet collectively, rare cancers contribute to 25% of all cancer diagnoses and over one third of all cancer deaths. This results in fewer treatment options available for those diagnosed with rare cancers, as well as the exclusion from clinical trials and biomarker studies.
A Phase II clinical trial (CA209-538) aimed to assess the use of Ipilimumab and Nivolumab in rare cancer patients. Patients included in the study were those diagnosed with rare upper GI tract malignancies, neuroendocrine tumours and gynaecological tumours. Blood samples were collected from patients pre- and post- combination immunotherapy commencement.
We have conducted a comprehensive study scoping all three tumour streams of rare cancer patients, using blood-based biomarker interrogations pre- and post- combination anti-CTLA-4 and anti-PD-1 immunotherapy. The scope of experiments involved multiparameter flow cytometry panels analysing PBMCs, as well as, antibody and secretome profiling using serum. The flow panels included groupings of immune markers and their activating and inhibiting molecules such as B cells, myeloid cells, lymphocytes, innate cells and immune checkpoint molecules. The antibody profiling included over 1600 tumour and autoantigens. Finally, the secretome profiling included 35 analytes covering immune stimulatory and inhibitory molecules, cytokines, chemokines, cell adhesion molecules and soluble HLA-G and -E molecules. This multi-pronged strategy resulted in a unique multiparameter biomarker signature which can predict clinical benefit and toxicity outcomes in patients receiving treatment, outperforming conventional biomarkers (tumour mutational burden, and PD-L1 tumour expression).
This research provides a personalised patient stratification approach for patients diagnosed with a rare cancer, a cohort of cancer patients who already face difficulties in obtaining access to immunotherapy. Moreover, given the tumour type heterogeneity seen among the cohort, identified predictive biomarkers are likely to be tumour agnostic, with potential applicability across the cancer immunotherapy field.