BMS-986253 / BMS - LARVOL DELTA

CA027-002: A Study of BMS-986253 in Combination With Nivolumab or Nivolumab Plus Ipilimumab in Advanced Cancers (clinicaltrials.gov) - P1/2 | N=281 | Completed | Sponsor: Bristol-Myers Squibb | Active, not recruiting ➔ Completed

Trial completion • Melanoma • Oncology • Solid Tumor • CXCL8

NICHE: Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: The Netherlands Cancer Institute | Not yet recruiting ➔ Recruiting

Checkpoint inhibition • Enrollment open • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

NICHE: Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer (clinicaltrials.gov) - P2 | N=268 | Recruiting | Sponsor: The Netherlands Cancer Institute | N=60 ➔ 268 | Trial completion date: Jan 2022 ➔ Dec 2024 | Trial primary completion date: Jun 2021 ➔ Dec 2024

Checkpoint inhibition • Enrollment change • Trial completion date • Trial primary completion date • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

NICHE: Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: The Netherlands Cancer Institute

Checkpoint inhibition • New P2 trial • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

NICHE: Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer (clinicaltrials.gov) - P2 | N=353 | Recruiting | Sponsor: The Netherlands Cancer Institute | N=268 ➔ 353 | Trial completion date: Dec 2024 ➔ Mar 2032 | Trial primary completion date: Dec 2024 ➔ Mar 2032

Checkpoint inhibition • Enrollment change • Trial completion date • Trial primary completion date • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor

NICHE: Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: The Netherlands Cancer Institute | Trial completion date: Jan 2020 ➔ Jan 2022 | Trial primary completion date: Jun 2019 ➔ Jun 2021

Checkpoint inhibition • Trial completion date • Trial primary completion date • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

NICHE: Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: The Netherlands Cancer Institute | Trial primary completion date: Jan 2019 ➔ Jun 2019

Checkpoint inhibition • Trial primary completion date • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Spark2: Neoadjuvant Targeting of Myeloid Cell Populations in Combination With Nivolumab in Head & Neck Ca (clinicaltrials.gov) - P2 | N=24 | Active, not recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting ➔ Active, not recruiting

Enrollment closed • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Platform Study of Neoadjuvant and Adjuvant Immunotherapy for Patients With Resectable Adenocarcinoma of the Pancreas (clinicaltrials.gov) - P2 | N=76 | Active, not recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial primary completion date: Oct 2025 ➔ May 2026

IO biomarker • Trial primary completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Nivolumab Combined With BMS-986253 in HCC Patients (clinicaltrials.gov) - P2 | N=13 | Terminated | Sponsor: NYU Langone Health | N=23 ➔ 13 | Completed ➔ Terminated; Study was terminated early by the drug sponsor due to slow accrual and a change in the company's drug development priorities

Enrollment change • Trial termination • Hepatocellular Cancer • Oncology • Solid Tumor

A novel anti-PD-L1/IL-8 bispecific antibody BP2402 enhances antitumor immunity and modulates inflammatory signaling in triple-negative breast cancer mice model. (PubMed, J Transl Med) - "These results indicate that dual targeting of PD-L1 and IL-8 pathways represents a promising therapeutic strategy for TNBC. The bispecific antibody approach offers superior therapeutic potential by simultaneously modulating immune checkpoints, inflammatory signaling, and angiogenesis, effectively addressing resistance mechanisms. Additional preclinical optimization and clinical studies are required to fully assess the therapeutic potential of this novel immunotherapeutic approach."

IO biomarker • Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CXCL8 • HAVCR2 • JAK1

The Interleukin-8-CXCR1/2 Axis as a Therapeutic Target in Peritoneal Carcinomatosis. (PubMed, Curr Oncol) - "IL-8 targeting agents such as monoclonal antibodies (BMS-986253) and small-molecule inhibitors (SX-682, AZD5069, navarixin) have shown efficacy in mitigating tumor growth and improving the efficacy of immune checkpoint inhibitors. In this review, we discuss the influence of the IL-8/CXCR1/CXCR2 axis within the peritoneal immune environment in PC and highlight recent work using IL-8 or CXCR1/CXCR2 blockade as a therapeutic strategy for PC. Continued research into the peritoneal immune microenvironment and the development of targeted therapies are essential for improving the management and prognosis of PC, potentially enhancing antitumor immunity and patient outcomes."

Journal • Review • Oncology • Peritoneal Cancer • CXCL8 • CXCR1 • CXCR2 • IL6

Platform Study of Neoadjuvant and Adjuvant Immunotherapy for Patients With Resectable Adenocarcinoma of the Pancreas (clinicaltrials.gov) - P2 | N=76 | Active, not recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting ➔ Active, not recruiting

Enrollment closed • IO biomarker • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Neoadjuvant immunotherapy of hepatocellular carcinoma: A single-institution experience at Mount Sinai. (ASCO 2025) - P2 | " We identified 17 patients from NCT04123379 (nivolumab alone or in combination with BMS-813160 or BMS-986253), 41 patients from NCT03916627 (cemiplimab alone or cemiplimab plus radiation), and 8 patients who received neoadjuvant nivolumab off protocol. Neoadjuvant immunotherapy with anti-PD-1 in patients with resectable HCC appears to be feasible with a generally acceptable safety profile. Further studies are needed to identify optimal immunotherapy regimens to be used in the neoadjuvant setting as well as optimal duration, and larger cohorts are needed to validate the correlation of pathological response with recurrence and survival."

Clinical • Chronic Obstructive Pulmonary Disease • Hepatocellular Cancer • Hepatology • Immunology • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor

Nivolumab Combined With BMS-986253 in HCC Patients (clinicaltrials.gov) - P2 | N=23 | Completed | Sponsor: NYU Langone Health | Active, not recruiting ➔ Completed | Trial completion date: Dec 2025 ➔ Jan 2025

Trial completion • Trial completion date • Hepatocellular Cancer • Oncology • Solid Tumor

Nivolumab and BMS-986253 for Hormone-Sensitive Prostate Cancer (MAGIC-8) (clinicaltrials.gov) - P1/2 | N=59 | Active, not recruiting | Sponsor: Mark Stein | Trial completion date: Jan 2025 ➔ Jan 2026

Trial completion date • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Spark2: Neoadjuvant Targeting of Myeloid Cell Populations in Combination With Nivolumab in Head & Neck Ca (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Apr 2026 ➔ Sep 2026 | Trial primary completion date: Apr 2025 ➔ Apr 2026

Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Platform Study of Neoadjuvant and Adjuvant Immunotherapy for Patients With Resectable Adenocarcinoma of the Pancreas (clinicaltrials.gov) - P2 | N=76 | Recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Aug 2026 ➔ May 2026

IO biomarker • Trial completion date • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

GCO 19-1754: Neoadjuvant Nivolumab with CCR2/5-inhibitor or Anti-IL-8) for Non-small Cell Lung Cancer (NSCLC) or Hepatocellular Carcinoma (HCC) (clinicaltrials.gov) - P2 | N=48 | Active, not recruiting | Sponsor: Icahn School of Medicine at Mount Sinai | Completed ➔ Active, not recruiting | Trial completion date: Nov 2023 ➔ Dec 2025 | Trial primary completion date: Nov 2023 ➔ Dec 2025

Enrollment closed • Trial completion date • Trial primary completion date • Hepatocellular Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

BMS-986253 Plus Nivolumab/Ipilimumab Fails to Boost Responses in Advanced Melanoma After Prior Anti–PD-(L)1 Therapy (OncLive) - P1/2 | N=281 | NCT03400332 | Sponsor: Bristol-Myers Squibb | "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."

P1/2 data • Melanoma

Platform Study of Neoadjuvant and Adjuvant Immunotherapy for Patients With Resectable Adenocarcinoma of the Pancreas (clinicaltrials.gov) - P2 | N=76 | Recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2025 ➔ Aug 2026 | Trial primary completion date: Dec 2024 ➔ Aug 2025

IO biomarker • Trial completion date • Trial primary completion date • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CD8 • GZMB • IL17A • PD-1 • TNFRSF9

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 (ESMO-IO 2024) - P1/2 | "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. Table: 121MO Arm AAnti–IL-8 + NIVO + IPI n=62 Arm BPBO + NIVO + IPI n=60 ORR, n (%) (95% CI) 9 (15)(6.9–25.8) 7 (12)(4.8–22.6) OR (95% CI) P 1.3 (0.4–3.6)0.68 Confirmed best overall response, n (%) CR 5 (8) 1 (2) PR 4 (6) 6 (10) SD 12 (19) 19 (32) PD 31 (50) 22 (37) Not determined 7 (11) 8 (13) Not reported 0 3 (5) Median PFS, months (95% CI) 2.1 (1.9–3.8) 3.3 (1.9–3.7) HR (95% CI) P 0.94 (0.61–1.45)0.74 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..."

Clinical • Combination therapy • Metastases • P1/2 data • Melanoma • Oncology • Solid Tumor • CXCL8

Spark2: Neoadjuvant Targeting of Myeloid Cell Populations in Combination With Nivolumab in Head & Neck Ca (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial primary completion date: Aug 2024 ➔ Apr 2025

Combination therapy • Surgery • Trial primary completion date • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Effects of In Vivo IL-8 Axis Blockade on Myeloid Derived Suppressor Cells (MDSC) in a Patient With High-Risk MDS and Excess Blasts (SOHO 2024) - P1/2 | "Based on safety data from early-phase trials investigating the anti-IL8 monoclonal antibody BMS-986253 in patients with unresectable solid tumors, we hypothesized that the addition of BMS-986253 to hypomethylating agents (HMA) is safe might enhance the efficacy of HMAs against MDS. Case Report: A 64-year-old female patient with treatment-refractory high-risk MDS and increased blasts (15-20%) was treated with combination oral decitabine-cedazuridine and the anti-IL-8 antibody in a phase 1 clinical protocol (NCT05148234)...CD45+CXCR1+ cells decreased by ~39%, whereas CD45+CXCR2+ increased. Collectively, the data suggest that blocking IL-8, even at low doses, can decrease the egress of MDSCs, which could have therapeutic implications in MDS patients and should be further investigated in clinical trials."

Myeloid-derived suppressor cells • Preclinical • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Solid Tumor • CD14 • CD33 • CEACAM8 • CXCL8 • CXCR1 • CXCR2 • ITGAM • PTPRC

GCO 19-1754: Neoadjuvant Nivolumab With CCR2/5-inhibitor or Anti-IL-8) for Non-small Cell Lung Cancer (NSCLC) or Hepatocellular Carcinoma (HCC) (clinicaltrials.gov) - P2 | N=48 | Completed | Sponsor: Icahn School of Medicine at Mount Sinai | N=36 ➔ 48 | Trial completion date: Sep 2024 ➔ Nov 2023 | Active, not recruiting ➔ Completed

Enrollment change • Trial completion • Trial completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor