515 Phase II biomarker study of BND-22 in combination with cemiplimab in patients with cholangiocarcinoma
Year: 2026
Type: conference-abstract
Abstract: Background The immune checkpoint landscape continues to expand beyond PD-1/PD-L1, with inhibitory receptors such as immunoglobulin-like transcript-2 (ILT2) emerging as promising therapeutic targets. ITL2 is broadly expressed on immune cells, including monocytes, dendritic cells, NK cells, and a subset of T-cells, 1 and exerts its immunosuppressive effects primarily through binding MHC class-I molecules, with high affinity for HLA-G.2 HLA-G is frequently overexpressed in solid tumors,3 where engagement of the HLA-G/ITL2 axis suppresses a broad spectrum of immune functions, including cytotoxicity, cytokine production, antigen presentation, phagocytosis and proliferation.4 5 ILT2 expression has been increased following anti-PD-1 therapy, identifying it as a potential mediator of resistance to checkpoint blockade6 and a compelling target for combination immunotherapy strategies.BND-22 is a first-in-class humanized IgG4 mAb that selectively targets ILT2 on NK/T cells, and macrophages, disrupting its interaction with HLA-G.6 Preclinical studies and a phase I trial7 8 demonstrated that BND-22 as a monotherapy and in combination with a PD-1 inhibitor enhanced anti-tumor activity, with evidence of dose-dependent immune activation. Building on this finding, we initiated a phase II biomarker study (NCT06651593) of BND-22 in combination with cemiplimab, a recombinant human IgG4/kappa anti–PD-1 mAb, to further understand immune biology and explore the tumor microenvironment.Methods An initial cohort of 10 patients with cholangiocarcinoma with prior immunotherapy exposure will be enrolled, with potential expansion of up to 10 additional patients based on emerging data.The dose of BND-22 is 10 mg/kg IV on Day 1 every 3 weeks (Q3W), based on the dose escalation trial (NCT04717375). The dose of cemiplimab is the FDA-approved dose of 350 mg IV on Day 1 Q3W, starting at C2D1. Each cycle = 21 days. The combination will be administered for a maximum of 24 months in the absence of progression or until progression, unacceptable toxicity, death, withdrawal of consent, or discontinuation. Biopsy tissues and blood samples for biomarker analyses will be collected at baseline, on treatment, and at progression (for patients with CR, PR, or SD≥6 months).The primary objective is 1) to identify biomarkers related to mechanism of action and predictors of response, resistance, and survival 2) evaluate the association between the biomarkers and outcomes. The secondary objective is to evaluate efficacy, safety, and tolerability of this combination; identify imaging characteristics predictive of response and toxicity; and evaluate TCR beta variable polymorphism and its relationship with immune-related adverse events.Enrollment is ongoing; 4 patients with cholangiocarcinoma have been treated.References Kirwan SE, Burshtyn DN. Killer cell Ig-like receptor-dependent signaling by Ig-like transcript 2 (ILT2/CD85j/LILRB1/LIR-1). J Immunol. 2005;175:5006–15.Shiroishi M, Tsumoto K, Amano K, Shirakihara Y, Colonna M, Braud VM, Allan DS, Makadzange A, Rowland-Jones S, Willcox B, Jones EY, van der Merwe PA, Kumagai I, Maenaka K. Human inhibitory receptors Ig-like transcript 2 (ILT2) and ILT4 compete with CD8 for MHC class I binding and bind preferentially to HLA-G. Proc Natl Acad Sci U S A. 2003;100:8856–61.Yan WH. Human leukocyte antigen-G in cancer: are they clinically relevant? Cancer Lett. 2011;311:123–30.Naji A, Menier C, Morandi F, Agaugue S, Maki G, Ferretti E, Bruel S, Pistoia V, Carosella ED, Rouas-Freiss N. Binding of HLA-G to ITIM-bearing Ig-like transcript 2 receptor suppresses B cell responses. J Immunol. 2014;192:1536–46.Barkal AA, Weiskopf K, Kao KS, Gordon SR, Rosental B, Yiu YY, George BM, Markovic M, Ring NG, Tsai JM, McKenna KM, Ho PY, Cheng RZ, Chen JY, Barkal LJ, Ring AM, Weissman IL, Maute RL. Engagement of MHC class I by the inhibitory receptor LILRB1 suppresses macrophages and is a target of cancer immunotherapy. Nat Immunol. 2018;19:76-+.Mandel I, Haves Ziv D, Goldshtein I, Peretz T, Alishekevitz D, Fridman Dror A, Hakim M, Hashmueli S, Friedman I, Sapir Y, Greco R, Qu H, Nestle F, Wiederschain D, Pao L, Sharma S, Ben Moshe T. BND-22, a first-in-class humanized ILT2-blocking antibody, promotes antitumor immunity and tumor regression. J Immunother Cancer. 2022;10.Perets R, Stemmer SM, Geva R, Golan T, Fakih M, Cohen JE, Lieu C, Jin Z, Lorusso P, Friedman I, Hakim M, Haves Ziv D, Hashmueli S, Mandel I, Ben Moshe T, Crawford N, Abbadessa G, Perez R, Wu M, Borad M. 990O Final results from phase I, first-in-human, dose escalation study of a first-in-class anti-ILT2 antibody, SAR444881, alone and with pembrolizumab or cetuximab, in patients with advanced solid tumors. Annals of Oncology 2024;35:S675.Perets R, Stemmer SM, Geva R, Golan T, Fakih MG, Cohen J, Lieu C, Zhaohui J, LoRusso P, Friedman I, Hakim M, Ziv DH, Hashmueli S, Mandel I, Moshe TB, Crawford N, Abbadessa G, Perez R, Wu M, Borad M. 623 Final results from phase 1, first-in-human, dose escalation study of a first-in-class anti-ILT2 antibody, SAR444881, alone and with pembrolizumab or cetuximab, in patients with advanced solid tumors. Journal for ImmunoTherapy of Cancer 2024;12.Trial Registration NCT06651593.Ethics Approval The US Food and Drug Administration and The University of Texas MD Anderson Cancer Center Institutional Review Board (IRB) approved the protocol (Federalwide Assurance Number 00000363 and Office of Human Research Protection IRB Registration Number: IRB00000121). In keeping with the Declaration of Helsinki and International Council for Harmonization Good Clinical Practice guidelines, all participants provided written informed consent before enrollment in this study.
Authors: Mohamed H Derbala, Camila Braganca Xavier, Cara L Haymaker, Maria Gabriela Raso, Luisa M Solis Soto, Bettzy Stephen, Hassan A Momin, Yali Yang, Serdar A Gurses, Ann M Cimo, Stephane Champiat, Tin-Yun Tang, Apostolia M Tsimberidou, Ecaterina E Dumbrava, Sarina A Piha-Paul, Natalia Ashtamker, Funda Meric-Bernstam, Milind Javle, Aung Naing
Institution: The University of Texas MD Anderson Cancer Center
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,490
OpenAlex ID: W7225325412
Cites:
Cited by:
Related to: