CA209-538 is a prospective multicentre Phase II clinical trial sponsored by the Olivia Newton-John Cancer Research Institute investigating the efficacy of combined immune checkpoint blockade (CTLA-4/ipilimumab and PD-1 blockade/nivolumab) in a range of rare cancers (NCT02923934, n=120). Participants received the anti-PD-1 antibody nivolumab and the anti-CTLA-4 antibody ipilimumab every three weeks for four doses, followed by nivolumab (3 mg/kg IV) every two weeks and continued for up to 96 weeks, until disease progression or unacceptable toxicity. While approximately 20% of the study population progressed on or before the first evaluation at 12 weeks, the entire trial population achieved an overall response rate (ORR) and the clinical benefit rate (CBR) of ~ 30% and 50% respectively.
Patients with rare cancers have limited therapeutic options, low survival and are often excluded from clinical trials and biomarker studies due to the low incidence (<6 per 100,000 individuals). However, while incidence is low for each individual rare cancer, collectively they comprise of almost 25% of all cancer diagnoses. To identify biomarkers for rare cancer patients responding to combination immunotherapy we evaluated baseline and on-treatment collected biospecimen including PBMCs, stool, sera/plasma and tumour tissue for markers of response including cancer-specific autoantibodies, cytokine levels, microbiome, PD-L1 status, baseline tumor gene-expression and tumour mutational burden (TMB).