The addition of BMS-986253, an anti-interleukin 8 (IL-8) monoclonal antibody, to nivolumab (Opdivo) and ipilimumab (Yervoy) did not improve responses or progression-free survival (PFS) in patients with advanced melanoma whose disease progressed on or after prior anti-PD-(L)1 therapy. These findings come from the final analysis of part 2 of the phase 1/2 CA027-002 trial (NCT03400332), presented at the 2024 ESMO Immuno-Oncology Congress. The results suggest that the combination does not offer a significant advantage over nivolumab and ipilimumab alone in this patient population.
Efficacy Outcomes
Patients treated with BMS-986253 plus nivolumab and ipilimumab (n = 62) experienced an overall response rate (ORR) of 14.5%, compared to 11.7% for those given nivolumab plus ipilimumab alone. This difference was not statistically significant (odds ratio, 1.3; 95% CI, 0.4-3.6; P = .6806). Complete response (CR) rates were 8.1% in the BMS-986253 arm and 1.7% in the control arm. Partial response rates were 6.5% and 10.0%, respectively. Stable disease (SD) was observed in 19.4% of patients in the BMS-986253 arm and 31.7% in the control arm. Progressive disease (PD) rates were 50.0% and 36.7%, respectively.
The median time to response was 1.9 months in the BMS-986253 arm versus 2.6 months in the placebo arm. The median duration of response was not applicable (NA; 95% CI, 4.07-NA; range, 4.1-18.5) in the BMS-986253 arm versus NA (95% CI, 5.29-NA; range, 4.6-15.5) in the placebo arm.
The median PFS was 2.1 months (95% CI, 1.9-3.8) in the BMS-986253 group versus 3.3 months (95% CI, 1.9-3.7) in the placebo group (HR, 0.94; 95% CI, 0.61-1.45; P = .74). The 6- and 12-month PFS rates in the BMS-986253 arm were 24% and 15%, respectively, compared to 22% and 12% in the placebo arm.
Study Design and Patient Population
The CA027-002 trial enrolled patients aged 18 years or older with histologically confirmed, unresectable, stage III or IV melanoma whose disease had progressed on or after anti-PD-(L)1 therapy. Patients were required to have received prior anti-PD-(L)1 therapy as their most recent line of treatment and had an ECOG performance status of 0 or 1. Prior anti-CTLA-4 therapy was not allowed. Patients were randomized 1:1 to receive either BMS-986253 plus nivolumab and ipilimumab or placebo plus nivolumab and ipilimumab.
Safety Profile
Treatment-related adverse events (TRAEs) of any grade occurred in 95.2% of patients in the BMS-986253 arm and 87.7% in the control arm. Grade 3/4 TRAEs were reported in 46.8% and 52.6% of patients, respectively. TRAEs led to treatment discontinuation in 22.6% of patients in the BMS-986253 group and 24.6% in the placebo group. Serious TRAEs occurred in 38.7% and 40.4% of patients, respectively.
The most common grade 3/4 TRAEs included diarrhea (BMS-986253 arm, 9.7%; placebo arm, 15.8%), colitis (6.5%; 12.3%), increased alanine aminotransferase levels (8.1%; 5.3%), increased aspartate aminotransferase levels (4.8%; 5.3%), and increased lipase levels (6.5%; 3.5%). One grade 5 TRAE was reported in each arm: renal failure in the experimental arm and hemophagocytic lymphohistiocytosis in the placebo arm.
Clinical Implications
According to lead study author Matteo Simonelli, MD, of the IRCCS Humanitas Research Hospital Humanitas University in Milan, Italy, these results further support the use of nivolumab plus ipilimumab for patients with melanoma who progress on anti-PD-[L]1 monotherapy.
