BMS-986253 Plus Nivolumab/Ipilimumab Fails to Boost Responses in Advanced Melanoma After Prior Anti–PD-(L)1 Therapy

Melanoma | Maris– stock.adobe.com

The addition of the anti–interleukin 8 (IL-8) monoclonal antibody BMS-986253 to nivolumab (Opdivo) and ipilimumab (Yervoy) did not lead to an improvement in responses or progression-free survival (PFS) compared with nivolumab plus ipilimumab alone in patients with advanced melanoma whose disease progressed on or after prior anti–PD-(L)1 therapy, according to data from the final analysis of part 2 of the phase 1/2 CA027-002 trial (NCT03400332).

Data presented at the 2024 ESMO Immuno-Oncology Congress showed that patients treated with BMS-986253 plus nivolumab and ipilimumab (n = 62) experienced an overall response rate (ORR) of 14.5% vs 11.7% for those given nivolumab plus ipilimumab alone (odds ratio, 1.3; 95% CI, 0.4-3.6; P = .6806). In the BMS-986253 arm, the complete response (CR), partial response, stable disease (SD), and progressive disease (PD) rates were 8.1%, 6.5%, 19.4%, and 50.0%, respectively. These respective rates were 1.7%, 10.0%, 31.7%, and 36.7% in the control arm.

No patients in either arm had SD for more than 6 months. In the BMS-986253 group, 4.8% of patients had a best response of non-CR/non-PD, and response was unable to be determined in 11.3% of patients. In the control arm, 1.7% of patients had a best response of non-CR/non-PD, 13.3% were unable to be evaluated for response, and best response was not reported in 5.0% of patients.

“These results further support the use of nivolumab plus ipilimumab for patients with melanoma who progress on anti–PD-[L]1 monotherapy,” lead study author Matteo Simonelli, MD, of the IRCCS Humanitas Research Hospital Humanitas University in Milan, Italy, said in a presentation of the data.

CA027-002 Overview

Part 2 of CA027-002 included patients at least 18 years of age with histologically confirmed, unresectable, stage III or IV melanoma whose disease progressed on or after anti–PD-(L)1 therapy. Prior anti–PD-(L)1 therapy needed to be the most recent line of treatment. Patients with BRAF V600E–mutated and wild-type disease were allowed to enroll, and patients needed to have an ECOG performance status of 0 or 1. No prior anti–CTLA-4 therapy was allowed.

Patients were randomly assigned 1:1 to receive 3600 mg of BMS-986253 once every 2 weeks plus 1 mg/kg of nivolumab once every 3 weeks and 3 mg/kg of ipilimumab once every 3 weeks for the first 12 weeks, followed by 3600 mg of BMS-986253 once every 2 weeks plus 480 mg of nivolumab once every 4 weeks; or placebo plus the same regimen of nivolumab and ipilimumab for the first 12 weeks, followed by placebo plus 480 mg of nivolumab once every 4 weeks.

Stratification factors included serum IL-8 levels (>10 pg/mL vs ≤10 pg/mL), BRAF V600E status (mutated vs wild-type), and peripheral lactate dehydrogenase (LDH) levels (>upper limit of normal [ULN] vs ≤ULN).

Blinded independent central review–assessed ORR per RECIST 1.1 criteria served as the trial’s primary end point. Secondary end points included PFS and safety.

The median age was 64.0 years in the experimental arm vs 63.5 years in the control arm. The majority of patients were male (BMS-986253 arm, 64.5%; placebo arm, 71.7%), White (90.3%; 88.3%), not Hispanic or Latino (67.7%; 68.3%), from Europe (75.8%; 56.7%), had an ECOG performance status of 0 (80.6%; 83.3%), had LDH levels no higher than the ULN (62.9%; 61.7%), did not harbor BRAF V600E mutations (79.0%; 78.3%), and did not have brain metastases (96.8%; 93.3%).

Additional Efficacy and Safety Data

The median time to response was 1.9 months in the BMS-986253 arm vs 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 vs 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 vs 3.3 months (95% CI, 1.9-3.7) in the placebo group (HR, 0.94; 95% CI, 0.61-1.45; P = .74). In the BMS-986253 arm, the 6- and 12-month PFS rates were 24% and 15%, respectively. These respective rates in the placebo arm were 22% and 12%.

Regarding safety, any-grade treatment-related adverse effects (TRAEs) occurred in 95.2% of patients in the BMS-986253 arm vs 87.7% of patients in the control arm. The rates of grade 3/4 TRAEs were 46.8% and 52.6%, respectively. TRAEs led to treatment discontinuation in 22.6% of patients in the BMS-986253 group vs 24.6% of patients in the placebo group. The rates of serious TRAEs were 38.7% and 40.4%, 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. One patient in the experimental arm had grade 5 renal failure, and 1 patient in the placebo arm had grade 5 hemophagocytic lymphohistiocytosis.

Disclosures: Dr Simonelli reported serving as an advisory board member for Incyte, Cytovia, and GSK; being an invited speaker for GSK and Bristol Myers Squibb; serving on a data monitoring committee for Sanofi; serving as a steering committee member for Celgene and Bristol Myers Squibb; and receiving travel grants from Roche, Sanofi, and Pfizer.

Reference

Simonelli M, Butler MO, Ascierto PA, et al. Anti–IL-8 (BMS-986253) in combination with nivolumab plus ipilimumab in patients with advanced melanoma: final analysis from the randomized part 2 of the phase 1/2 CA027-002 study. Presented at: 2024 ESMO Immuno-Oncology Congress; December 11-13, 2024; Geneva, Switzerland. Abstract 121MO.