Update of OpACIN and OpACIN-neo trials indicates benefit of neoadjuvant immunotherapy in patients with stage IIIB / IIIC melanoma

Update data on recurrence-free survival were evaluated in the OpACIN and OpACIN-neo trials, which were presented at AACR 2020

Update data on 36- and 18-month recurrence-free survival (RFS) from the OpACIN and OpACIN-neo studies were presented during the AACR 2020.

The OpACIN phase 1b trial compared ipilimumab + neoadjuvant nivolumab versus ipilimumab + nivolumab. Twenty patients with stage IIIB / IIIC melanoma were randomized to receive 4 cycles of ipilimumab (IPI) 3 mg / kg + nivolumab (NIVO) 1 mg / kg adjuvant versus 2 cycles of IPI + neoadjuvant NIVO in the same dose followed by 2 cycles of IPI + NIVO adjuvant.

In the OpACIN-neo trial, three different dosing schedules of ipilimumab with neoadjuvant nivolumab were evaluated in 86 patients randomized to 2 cycles:
• Arm A: 2 cycles of IPI 3 mg / kg + NIVO 1 mg / kg every 3 weeks (n = 30)
• Arm B: 2 cycles of IPI 1 mg / kg + NIVO 3 mg / kg every 3 weeks (n = 30)
• Arm C: 2 cycles of IPI 3 mg / kg every 3 weeks followed immediately by 2 cycles of NIVO 3 mg / kg every 3 weeks (n = 26).

The pathological response was defined as <50% of viable tumor cells and centrally reviewed blindly by a pathologist. RFS rates were estimated using the Kaplan-Meier method.

After a mean follow-up of 36 months for OpACIN and 18 months for OpACIN-neo, only 1 out of 71 patients (1.4%) relapsed on neoadjuvant therapy with pathological response versus 15 out of 23 patients (65.2%) without pathological response. In the OpACIN trial, the estimated recurrence-free survival (RFS) rate at 3 years for the neoadjuvant arm was 80% (95% CI: 59% – 100%) versus 60% (95% CI: 36% – 100%) for the adjuvant arm.

The median RFS was not achieved in any arm of the OpACIN-neo trial. The estimated rate of RFS at 18 months was 85% (95% CI: 78% – 93%) for all patients; 90% (95% CI: 80% – 100%) for arm A; 82% (95% CI: 70% – 98%) for arm B; and 83% (95% CI: 70% – 100%) for arm C.

The translational analysis showed that the mutational tumor load and the expression score of the interferon-γ gene in the baseline, separately and combined, can function as predictors of response.

OpACIN showed for the first time a potential benefit of neoadjuvant versus adjuvant immunotherapy. OpACIN-neo confirmed the high pathological response rates achieved with IPI + NIVO in neoadjuvance. Both trials reinforce that the pathological response may be a predictor of RFS.

References:
Blank, CU et al. 3412 – 36-months and 18-months relapse-free survival after (neo)adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma patients – update of the OpACIN and OpACIN-neo trials. Session MS.IM02.02 – Combination Immunotherapies
https://www.abstractsonline.com/pp8/#!/9045/presentation/6903