Background: There are limited data regarding the best sequence of targeted and immunotherapy in patients (pts) with BRAF-mutant melanoma. Some studies suggest lower activity of immunotherapy after BRAF/MEK inhibitors (BRAF/MEKi), but there are no data examining BRAF/MEKi after immunotherapy. Methods: Consecutive patients with BRAF-mutant metastatic melanoma from 6 centers treated with 1 or more lines of immunotherapy then subsequent BRAF/MEKi were identified. Disease characteristics, treatment details, RECIST response and survival data were retrospectively examined. If pts ceased BRAF/MEKi for toxicity prior to first response assessment, response was deemed progressive disease (PD). Results: 79 pts were included, with V600E (85%), V600K (13%), V600M (1%) and V600R (1%) mutations. 56% pts were treated with first-line ipilimumab, 21% with PD1 antibodies, 15% with combination ipilimumab/nivolumab, and 5% with other PD1 combinations. Median duration of immunotherapy was 10.9 weeks, and best response was partial response (PR) in 11%, stable disease (SD) in 17%, and PD in 72% pts. 20% of pts had 1 or more further lines of systemic treatment prior to BRAF/MEKi. At commencement of BRAF/MEKi, median age was 60 years, 68% were stage M1c, 25% had brain metastases, 57% had elevated LDH, 24% were ECOG 2/3. Median interval from last dose of immunotherapy was 6 weeks. 55 (70%) pts received combination BRAF+MEKi, 22 (28%) BRAFi alone, and 2 (3%) MEKi alone. 10/79 (13%) pts ceased BRAF/MEKi due to toxicity, 2 prior to first response, and median treatment duration was 21 weeks. 59% pts had a RECIST response (5% CR), 11% had SD and 29% had PD. Median PFS was 4.4 months (3.5 - 6.2). 65% pts had subsequent treatment, including PD1 antibodies in 50%. Median OS from BRAF/MEKi commencement was 18.0 months (14.6 - 40.3), and 39% were alive at 3 years. In the 35 (44%) pts that had received prior PD1 antibodies, the response rate was 66%, median PFS 4.1 months (2.4 - 6.8) and median OS 13.6 months (10.2 – NR). Conclusions: BRAF/MEKi have efficacy in pts previously treated with immunotherapy. Despite pts having more adverse disease characteristics than seen in first line trials, response rates may be similar, however PFS appears shorter.