121MO Anti-IL-8 (BMS-986253) in combination with nivolumab (NIVO) plus ipilimumab (IPI) in patients (pts) with advanced melanoma: Final analysis from the randomized part 2 of the phase I/II CA027-002 study.

Simonelli M, Butler MO, Ascierto PA, Long GV, Calvo E, Garcia VM, Gebhardt C, Grob JJ, Haydon AM, Quereux G, Walker J, Kumar M, Chakraborty D, Zhu X, Melero I. Immuno-Oncology and Technology, 24(Dec 2024), https://doi.org/10.1016/j.iotech.2024.100750.

Abstract

Background:

Elevated serum IL-8 is associated with increased tumour burden, immunotherapy resistance, and poor outcomes in many solid tumour types. Low IL-8 correlates with improved response to checkpoint inhibitors. Anti–IL-8 (BMS-986253) is a fully human IgG1κ mAb. Anti–IL-8 +/– NIVO demonstrated tolerability in pts with selected advanced cancers. Here, we report the final analysis from part 2 of CA027-002, a randomized phase 2 study of anti–IL-8 + NIVO + IPI vs placebo (PBO) + NIVO + IPI in pts with advanced melanoma resistant to PD-(L)1 blockade.

Methods: 

Pts with unresectable, stage III/IV melanoma who had progressed on/after anti–PD-(L)1 agents as their most recent therapy enrolled. No prior anti–cytotoxic T lymphocyte antigen-4 therapy was allowed. Pts were randomized to anti–IL-8 3600 mg IV Q2W + NIVO 1 mg/kg IV Q3W + IPI 3 mg/kg IV Q3W for 4 doses followed by anti–IL-8 3600 mg IV Q2W + NIVO 480 mg IV Q4W (arm A) or PBO + NIVO + IPI followed by PBO + NIVO (arm B). Primary endpoint was ORR by blinded independent central review.

Results: 

122 pts were randomized to arm A (n=62) or B (n=60). ORR in arm A and B was 15% and 12% (OR 1.3 [95% CI, 0.4–3.6] P=0.68), including complete responses in 5 pts and 1 pt, respectively (Table). Median (95% CI) PFS in arm A and B was 2.1 (1.9–3.8) and 3.3 (1.9–3.7) months (HR 0.94 [95% CI, 0.61–1.45]; P=0.74); 12-month PFS rates were 15% and 12%, respectively. The most common grade ≥3 TRAEs (≥10% in either arm A/B) were diarrhoea (10%/16%), and colitis (6%/12%). TRAEs leading to treatment discontinuation occurred in 14 (23%) and 14 (25%) pts in arm A and B.

CR, complete response; HR, hazard ratio; OR, odds ratio; ORR, objective response rate; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease.

Conclusions: 

In this study population, the addition of anti–IL-8 to NIVO + IPI was well tolerated, but no statistically significant difference for the primary endpoint of ORR or the secondary endpoint of PFS was observed in patients with advanced melanoma who had progressed on/after anti-PD-(L)1 therapy.