Background: Durable unmaintained remissions are consistently observed in a small percentage of patients with metastatic melanoma (mM) treated with HD IL-2. Vemurafenib therapy gives rise to a high response rate in BRAF-V600 (BRAF) mutated melanoma patients, but these are relatively short-lived; thus using both drugs in sequence may complement the individual strengths of each therapy. We report the early efficacy and safety results for the PROCLIVITY01 clinical trial of sequenced vemurafenib and HD IL-2. Methods: The primary objective is to assess the CR rate at 10 wks ±3 (assessment 1) and 26 wks ± 3 (assessment 2) from start of HD IL-2. Trial patients were IL-2 eligible and BRAF mutant positive. Cohort 1 patients were treatment naïve and on trial received vemurafenib 960 mg BID for 6 weeks prior to HD IL-2. Cohort 2 patients received vemurafenib for 7-18 weeks prior to enrollment. Both cohorts received HD IL-2 at 600,000 IU/kg every 8 hours for up to 14 doses on days 1-5 and days 15-19. Vemurafenib was held during HD IL-2 treatment. Results: A total of 53 patients received vemurafenib (cohort 1, N = 38); cohort 2 (N = 15). Of these, 40 had assessment 1 and 15 had assessment 2. The overall response rate is14.8% and disease control rate is 51.9% for cohort 1, assessment 1 (n = 27), and 15.4 and 69.2% for cohort 2 (n = 13), respectively. An independent safety committee did not raise safety concerns with the sequencing of these two drugs and patients experienced toxicities as anticipated for IL-2 or vemurafenib. There were no treatment-related deaths. A shift in the melanoma treatment landscape during this trial adversely affected accrual, and led to early trial closure. Conclusions: Vemurafenib given in sequence with HD IL-2 did not change the known toxicity profile for either drug. Early efficacy results reveal low response rates for vemurafenib. Durability of response and long term survival will be reported as patients continue to be followed in the PROCLAIM IL-2 database. Clinical trial information: NCT01683188