BMS-986253

P2, N=24, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial primary completion date: Aug 2024 --> Apr 2025

P1/2, N=2, Terminated, National Cancer Institute (NCI) | N=200 --> 2 | Trial completion date: Jul 2025 --> Jul 2023 | Active, not recruiting --> Terminated; Company closed the trial.

P1, N=50, Recruiting, Jason J. Luke, MD | Suspended --> Recruiting

P2, N=48, Completed, Icahn School of Medicine at Mount Sinai | N=36 --> 48 | Trial completion date: Sep 2024 --> Nov 2023 | Active, not recruiting --> Completed

P1, N=50, Suspended, Jason J. Luke, MD | Trial completion date: Dec 2026 --> May 2027 | Recruiting --> Suspended | Trial primary completion date: Dec 2025 --> May 2024

P2, N=24, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial primary completion date: Apr 2024 --> Aug 2024

P1/2, N=372, Active, not recruiting, Bristol-Myers Squibb | Recruiting --> Active, not recruiting

P1/2, N=60, Active, not recruiting, Mark Stein | Phase classification: P1b/2 --> P1/2 | Trial completion date: Dec 2023 --> Jan 2025 | Trial primary completion date: Oct 2023 --> May 2024

P1/2, N=200, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | Trial completion date: Jan 2025 --> Jul 2025 | Trial primary completion date: Jan 2025 --> Jul 2023

No abstract available

P1, N=50, Recruiting, Jason J. Luke, MD | Trial completion date: Jul 2026 --> Dec 2026 | Trial primary completion date: Jul 2023 --> Dec 2025

P2, N=76, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Jun 2024 --> Dec 2025 | Trial primary completion date: Jun 2023 --> Dec 2024

P1/2, N=372, Recruiting, Bristol-Myers Squibb | Trial completion date: Jun 2024 --> Nov 2025 | Trial primary completion date: Feb 2023 --> Apr 2024

Preliminary and durable antitumor activity was observed across a range of doses/regimens. These findings support further evaluation of BMS-986253 in pts with melanoma following anti–PD-(L)1 therapy in the phase 2 part of this study.

Methods This phase IIa multi-cohort, two-stage trial was designed to assess the clinical efficacy of BMS-813160 (CCR2/5 inhibitor) and BMS-986253 (anti-IL8 antibody) in patients with resectable NSCLC and HCC. Deep immune monitoring will be performed using multiplex and single-cell analysis platforms to define the immunodynamic effects of the therapies. Trial Registration NCT04123379

The present study aims to evaluate safety and preliminary efficacy of combining BMS-986253 with nivolumab and SBRT in patients with advanced solid tumors, chiefly melanoma (MEL) and renal cell carcinoma (RCC). Blocking IL8 in conjunction with anti-PD1 therapy and SBRT is a rational, biomarker-driven approach that may overcome resistance and broaden immunotherapy benefit in patients for whom anti-PD1 therapy is inadequate. This trial is registered at ClinicalTrials.gov, NCT04572451.

Secondary objectives include PFS by BICR in all randomized patients, overall response rates by BICR per RECIST v1.1, overall survival, safety, pharmacokinetic profile, immunogenicity of BMS-986253, and associations of baseline factors with response. Recruitment will continue until ≈170 patients are enrolled.

P2, N=76, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Phase classification: P1/2 --> P2

To test the importance of myeloid attraction and signaling to CTC survival in the portal blood, humanized monoclonal blocking antibodies to CSF1R (BMS-986227, Cabralizumab), IL-8 (BMS-986253), and mouse monoclonal antibodies to IL-34 (1D12, Abcam) were used to inhibit CTC/M-FB signaling pathways. Blocking IL-8 signaling from CTC allowed myeloid cells to produce their own IL-8 and avoid being drawn to CTC and their CSF1/IL-34/CSF2 influence on myeloid differentiation. Without myeloid cell attraction and differentiation, clusters don’t form, leaving CTC unaided by M-FB, and myeloid cells differentiating away from immunosuppressive, pro-tumor phenotypes. Such treatments could lead to enhanced anti-tumor myeloid cell responses and suppression of CTC survival.

P2, N=43, Terminated, Matthew Dallos | N=138 --> 43 | Trial completion date: Sep 2022 --> Mar 2021 | Recruiting --> Terminated | Trial primary completion date: Sep 2021 --> Mar 2021; Interim analysis indicated that futility boundary was reached.

P1/2, N=76, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Feb 2023 --> Jun 2024 | Trial primary completion date: Jun 2022 --> Jun 2023

The combination of BMS-986253 and nivolumab was safe in patients with advanced solid tumors . We will include 20 patients with MEL and RCC and compare against a historical benchmark of 20% ORR as sufficient signal of activity for further study . ORR will be assessed for association with serum IL-8 levels and radiation-induced changes in peripheral blood T cell populations.

P1/2, N=372, Recruiting, Bristol-Myers Squibb | Active, not recruiting --> Recruiting | Trial completion date: Nov 2023 --> Jun 2024 | Trial primary completion date: Nov 2023 --> Feb 2023

P2, N=138, Recruiting, Matthew Dallos | Not yet recruiting --> Recruiting

P2, N=138, Not yet recruiting, Matthew Dallos