1096P Prolonged follow-up confirms durability of favorable outcomes after neoadjuvant ipilimumab plus nivolumab in melanoma

A paradigm shift in the treatment of resectable stage III melanoma is expected, given the superior results of neoadjuvant (neoadj) immune checkpoint inhibition (ICI) in the SWOG S1801 trial and with the 1st phase III trial (NCT04949113) on its way. In this rapidly evolving field, long-term outcomes of neoadj ICI are scarce. Here we report the 4- and 6-yr survival update of the OpACIN and OpACIN-neo. In the randomized OpACIN trial, 20 patients (pts) with resectable stage III melanoma were treated with ipilimumab (IPI) 3mg/kg + nivolumab (NIVO) 1mg/kg; in the adjuvant (adj) arm 4 cycles after therapeutic lymph node dissection (TLND) and in the neoadj arm 2 cycles before and 2 after TLND. In the OpACIN-neo trial, 86 pts were randomized between neoadj IPI 3mg/kg + NIVO 1mg/kg (2x; arm A), IPI 1mg/kg + NIVO 3 mg/kg (2x; arm B) and IPI 3mg/kg (2x) > NIVO 3mg/kg (2x; arm C), followed by TLND without adj therapy. Event-free survival (EFS) was defined as time from randomization to progression, recurrence or death. Median follow-up (FU) for OpACIN was 84.0 mo. Estimated 6-yr EFS was 60% for both the adj and neoadj arm, while OS was 70% and 90% respectively. Only 1 recurrence has been observed after the 3-yr landmark. Median FU for OpACIN-neo was 60.7 mo. Estimated 4-yr EFS was 80% (see table for EFS/OS). After the 3-yr landmark, 1 new recurrence was observed and 1 non-melanoma related death. Major- and partial pathological responders (MPR/pPR) had 4-yr EFS rates of 96% and 92%, versus 33% in non-responders (pNR). Combining data from both trials, the median time to recurrence was 6.2 mo for the 16 pts that relapsed after pNR, while this was 37.7 mo for the 3 pts that relapsed after MPR/pPR.Table: 1096P6-year EFS (95% CI)6-year OS (95% CI)OpACIN – adjuvant60% (36-100)70% (47-100)OpACIN - neoadjuvant60% (36-100)90% (73-100)4-year EFS (95% CI)4-year OS (95% CI)OpACIN-neo80% (43-89)92% (86-98)Arm A87% (75-100)90% (80-100)Arm B77% (63-93)93% (85-100)Arm C77% (62-95)92% (83-100) Open table in a new tab Although the EFS rates are similar for the neoadj and adj arms after 6 yrs in the OpACIN trial, the favorable EFS and OS rates observed in the larger OpACIN-neo support the durability of response to neoadj IPI plus NIVO. The pathological response may serve as predictor for long-term outcome.