The presentation will focus on the outcome of CA209-538, an immunotherapy trial using combined anti-PD-1/CTLA-4 checkpoint blockade in patients with advanced rare cancers.
Patients with rare cancers represent 25 % of all cancer diagnoses and have inferior survival outcomes compared to patients with more common malignancies. No treatments, including immunotherapies, have formally been evaluated in this patient population. Combination immunotherapy with the anti-PD-1 antibody nivolumab and the anti-CTLA-4 antibody ipilimumab has demonstrated superior clinical efficacy in patients with advanced melanoma and other tumour types compared to anti-PD-1 monotherapy, justifying evaluation of this combination in rare cancers.
CA 209-538 was a multicentre phase 2 study enrolling patients with advanced rare upper gastrointestinal, neuroendocrine and gynaecological cancers. Patients received nivolumab and ipilimumab intravenously at a dose of 3mg/kg and 1mg/kg respectively every three weeks for four doses. Thereafter treatment was continued with nivolumab monotherapy at a dose of 3mg/kg every two weeks until disease progression or a maximum of two years. The primary endpoint was the proportion of patients with disease control at week 12 (complete response, partial response or stable disease).
One-hundred twenty patients were enrolled and received at least one dose of study treatment. The objective response rate in the radiologically evaluable population was 33% and 34% of patients obtained stable disease leading to disease control in 2/3 of the study population. Responses were observed across all three tumour cohorts with the majority of responses being ongoing. Severe immune related toxicity affected 1/3 of the study population in keeping with previously reported clinical trials using the same dosing regimen. Ongoing biomarker research revealed that tumour mutational burden had no predictive value in this patient population treated with combined anti-PD-1/CTLA-4 blockade.
Overall, ipilimumab and nivolumab combination treatment leads to durable responses in a range of advanced rare malignancies. An ongoing follow up trial, MoST-CIRCUIT/CA209-6D6 seeks to confirm these findings in a larger patient population of selected rare cancers.