Aims – To determine if a new combination of existing drugs, azacitidine and carboplatin can be used as a priming regime for metastatic melanoma to be re-challenged with Ipilimumab and Nivolumab.
Methods – The Phase 1b treatment regime consisted of 2 cycles of azacitidine and carboplatin over 6 weeks followed by 2 cycles of azacitidine and carboplatin combined with Ipilimumab and Nivolumab for 6 weeks. Ipilimumab and Nivolumab was then given in combination for 24 months. RECIST 1.1 and iRECIST were used to determine complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) and best overall response rate (BOR) after i) 2 cycles of priming (azacitidine and carboplatin) and ii) after 2 and 4 cycles of immunotherapy induction (ipilimumab and nivolumab), respectively.
Results – Patient 1 is a 70 year old female with acral lentiginous vulval metastatic melanoma with primary resistance to combination Ipilimumab and Nivolumab. Patient 1 had SD after 2 cycles (6 weeks) of priming and iUPD after 2 further cycles of priming and ipilimumab/nivolumab (12 weeks). A PR was achieved after an additional 2 cycles of ipilimumab/nivolumab (week 20) that was maintained until week 56 when a CR occurred. The CR remains ongoing. Patient 2 is a 75 year old male with metastatic melanoma with primary resistance to Ipilimumab and Nivolumab. Patient 2 had SD after 2 cycles of priming, followed by a PR (37.9%) after 4 cycles (12 weeks) that has steadily increased to PR (-78%) at 56 weeks. No treatment related grade 3 or 4 adverse events have been reported.
Conclusions – The two cases reported here provide evidence that sequential treatment with azacitidine and carboplatin can “prime” for immunotherapy rechallenge with Ipilimumab and Nivolumab, via stabilisation and decrease in the disease burden and re-establishment of immune sensitivity.