1112P Five-year survival after intermittent targeted therapy and anti-PD1 in stage IV melanoma: An update of the IMPemBra trial

IMPemBra was the first trial testing intermittent, short-term, dabrafenib and trametinib (DT) plus pembrolizumab (PEM) in patients with stage IV melanoma, with the concept of inducing stronger immune infiltration in the tumor, translating in better long-term outcome. The adverse event (AE) rate of intermittent DT was lower than for continuous triple therapy. While addition of DT only slightly increased the best overall response from 75% to 88%, the 3-year progression free survival (PFS) and overall survival (OS) was higher for the DT+PEM cohorts as compared to PEM only (53% vs 25%, and 64% vs 33%, respectively), no statistically significant differences were found probably due to small patient cohorts. Here we present the updated 5-year PFS and OS data from patients enrolled in the IMPemBra trial. 32 treatment-naïve patients with stage IV melanoma harboring a BRAFV600E/K mutated melanoma were enrolled. All patients started with 2 cycles of PEM 200mg (Q3W), followed by randomization to either PEM monotherapy (cohort 1); PEM in combination with either dabrafenib (D) 150 mg BID + trametinib (T) 2mg QD intermittent for 2x1 week (cohort 2), 2x2 weeks (cohort 3) or continuously for 6 weeks (cohort 4). From week 12 and onwards, all cohorts continued PEM for a maximum of in total 2 years. With a median follow-up of 59.6 months, the estimated 5-year RFS and OS rates were 25% and 50% in cohort 1, 63% and 63% in cohort 2, 38% and 75% in cohort 3, and 60% and 75% in cohort 4, respectively, as shown in the table. We observed no differences in the quantity and type of subsequential therapies between the cohorts. No new safety signals were identified.Table: 1112P5-year clinical outcomes5-year PFS (95% CI)5-year OS (95% CI)All patients (n=32)46% (32.5-67.3)66% (51.1-84.3)Cohort 1 (n=8)25% (7.5-83.0)50% (25.0-100)Cohort 2 (n=8)63% (36.5-100.0)63% (36.5-100)Cohort 3 (n=8)38% (15.3-91.7)75% (50.3-100)Cohort 4 (n=8)60% (33.1-100)75% (50.3-100)Subsequential therapiesSubsequential treatmentAnti-PD1Anti-CTLA-4Anti-CTLA-4 + anti-PD1Targeted therapySurgeryOtherAll patients18 (56%)6 (33%)2 (11%)7 (39%)14 (78%)2 (11%)1 (6%)Cohort 16 (75%)1 (13%)1 (13%)3 (38%)5 (63%)1 (13%)Cohort 23 (38%)2 (25%)3 (38%)Cohort 35 (63%)3 (38%)3 (38%)1 (13%)Cohort 44 (50%)2 (25%)1 (13%)2 (25%)3 (38%)1 (13%) Open table in a new tab This update from the IMPemBra trial confirms the previous findings indicating that the addition of short-term DT to PEM can induce long-lasting responses upon PEM that appears to be superior compared to PEM monotherapy. This improved PFS translated also into a promising increase in 5-year OS compared to PEM in first line therapy.