Final results of the phase III OCTAVA trial: Clinical benefit of low-dose anti–CTLA-4 plus anti–PD-1 combination vs anti–PD-1 monotherapy in unresectable or metastatic melanoma.

9544 Background: BCD-217-2/OCTAVA is an international, multi-center, randomized, double-blind, placebo-controlled phase III study conducted to assess the efficacy and safety of nurulimab +prolgolimab (nuru + prolgo ) combination therapy with continued prolgolimab therapy compared to prolgolimab monotherapy at the 1st line treatment of patients (pts) with unresectable or metastatic melanoma (un/mM). BCD-217 is a fixed-dose combination of nurulimab (aCTLA-4, 5 mg/ml) and prolgolimab (aPD-1, 15 mg/ml) which was recently approved for this indication in Russia and Belarus. Here we present efficacy results based on 24 mos of therapy. Methods: Treatment-naïve pts with un/mM (stage IIIC–IV) were randomized 1:1 to two arms. The nuru+prolgo arm received a combo of nurulimab (1 mg/kg) and prolgolimab (3 mg/kg) at 0.2 ml/kg Q3W for the first four infusions. The prolgo arm received prolgolimab monotherapy (3 mg/kg Q3W) for the first four infusions. Both arms then received prolgolimab maintenance therapy for up to two years. The primary endpoint of the study was PFS. Results: 271 pts were randomized to nuru+prolgo (n=135) or prolgo monotherapy (n=136) arms. After a median follow-up of 24.7 mos the mPFS was 15.4 (95% CI 8.4; NA) mos in the nuru+prolgo arm and 8.3 (95% CI 4.2; 14.8) mos in the prolgo monotherapy arm (HR 0.696, 95% CI 0.502; 0.965), iRECIST, ITT population). The PFS benefit was consistent per RECIST 1.1 (HR 0.717, 95% CI 0.533; 0.964). ORR, DCR and TTR were also higher in nuru+prolgo arm. mOS was not reached in both groups (HR 0.836, 95% CI 0.495; 1.41). 24-mos OS was 76.1% in nuru+prolgo arm and 71.7% in prolgo arm respectively. The mDOR was also not reached in any arm, meaning that more than half of the pts who responded to therapy maintained their response until the end of the FU period. Grade ≥3 treatment-related AEs occurred in 17.8% of pts (nuru+prolgo) vs 13.2% (prolgo). Gr ≥3 irAEs were 14.1% vs 5.1%, respectively (p=0.0126). Any-grade irAEs were reported in 51.9% vs 33.8% of cases (p=0.0027). Treatment discontinuation due to AEs was 11.1% vs 5.1%. Conclusions: The OCTAVA trial results demonstrated a statistically significant and clinically meaningful improvement in PFS for the 1st line low-dose nuru + prolgo combination followed by prolgo maintenance, compared to prolgo monotherapy, in patients with unresectable or metastatic melanoma. This efficacy benefit was accompanied by manageable rate of immune-related AE, consistent with the known profile of CTLA-4/PD-1 combinations. These results support the use of the nuru + prolgo regimen as a valuable 1st line treatment option for this population. Clinical trial information: NCT05732805 .