cabiralizumab (BMS-986227)

P2, N=13, Terminated, 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

Actualization of a patient-specific I-O combination treatment selection strategy is feasible, however, determination of de novo integral biomarker thresholds of novel I-O targets to facilitate effective treatment of PD-1-refractory cancer remains fraught. These data emphasize the difficulty of integral biomarker development for I-O in translating from immunotherapy treatment-naïve biospecimens to the selection of patients in the PD-1-refractory state.

P2, N=23, Completed, NYU Langone Health | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Jan 2025

P1, N=42, Completed, Yale University | Active, not recruiting --> Completed | Trial completion date: Oct 2027 --> May 2024

P2, N=4, Completed, University of Michigan Rogel Cancer Center | Active, not recruiting --> Completed

Higher anti-CSF1R doses are inferior to lower doses in a preclinical model, inducing a suppressive macrophage population, and potentially explaining the disappointing results observed in patients. While it is impossible to directly infer human doses from murine studies, careful intra-species evaluation can provide important insight. Cabiralizumab dose optimization is necessary for this patient population with limited treatment options.

LM-SBRT did not significantly increase the risk for hepatotoxicity in patients receiving ICI when respecting the above dose constraints. Risk for hepatotoxicity appears to be driven by dual agent ICI and underlying liver disease.

Pts with TGCT not amenable to surgery who received prior anti-CSF1/CSF1R therapy (including pexidartinib, cabiralizumab, or vimseltinib) were enrolled and treated with vimseltinib 30 mg twice weekly (recommended phase 2 dose). Longer follow-up demonstrated that vimseltinib continued to be well tolerated with a manageable safety profile in pts with TGCT not amenable to surgery who received prior anti-CSF1/CSF1R therapy. Antitumor activity continued to improve in this pretreated population, with an increased ORR. At week 25, all responders experienced ≥30% reductions in worst and average pain.

P2, N=206, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed | Trial completion date: Oct 2023 --> Jun 2023 | Trial primary completion date: Oct 2023 --> Jun 2023

Pexidartinib is the first CSF-1 receptor inhibitor approved for the treatment of TGCT. Here, we discuss various available treatment strategies and ongoing investigations and trials targeting diffuse TGCT, which include nilotinib, lacnotuzumab, cabiralizumab, vimseltinib, and emactuzumab.

P1/2, N=15, Active, not recruiting, Washington University School of Medicine | Recruiting --> Active, not recruiting | N=31 --> 15 | Trial completion date: Jun 2027 --> May 2026 | Trial primary completion date: Apr 2024 --> Mar 2023

P1, N=60, Completed, University of Chicago | Active, not recruiting --> Completed