ulocuplumab (BMS-936564) / BMS - LARVOL DELTA

Application of CXCR4-based NIR-II fluorescent probe in emergency intraoperative navigation for colorectal cancer (SNMMI 2026) - "Ulocuplumab (BMS-936564) is a human IgG4 monoclonal antibody targeting CXCR4 and has been demonstrated to have good biological safety and long tumor retention time... Ulocumab-IRDye800CW probe can quickly and specifically "light up" CXCR4-highly expressed CRC under emergency conditions, realizing real-time NIR-II fluorescence navigation, and providing a feasible new strategy for improving R0 resection rate in emergency surgery and reducing complications and recurrence rates."

Colorectal Cancer • Oncology • Solid Tumor • CXCR4

Harnessing VLPs and nanodiscs to unlock antibody discovery for challenging membrane proteins (AACR 2026) - "Using this system, KACTUS successfully presented the full-length STEAP1 protein (a prostate-cancer-associated antigen) and demonstrated specific binding to the therapeutic antibody Vandortuzumab with an EC₅₀ of 89.8 ng/mL...In addition, KACTUS developed CXCR4 VLP immunogens that generated functional antisera and monoclonal antibodies capable of ligand-blocking comparable to the commercial CXCR4 antibody Ulocuplumab...Together, these results demonstrate that the KACTUS VLP and nanodisc platforms deliver native-like, bioactive MP-TMPs suitable for antibody generation, ligand binding, and structural interrogation. This integrated technology provides a powerful solution to overcome long-standing challenges in membrane-protein immunization and screening, paving the way for next-generation therapeutic antibody discovery."

Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CXCR4 • STEAP1

Toward optimizing CXCR4 inhibition with beta adrenergic blockade to enhance chemotherapy response in acute myeloid leukemia (AACR 2024) - "The CXCR4 inhibitor plerixafor is used to increase mobilization of peripheral blood stem cells in combination with filgrastim...These have included use of plerixafor with 7+3 or MEC, BL-8040 with cytarabine, and ulocuplumab with MEC...The objective of this preclinical study is to identify the AML patient population most likely to respond to CXCR4 inhibition, and the role of combined beta-adrenergic blockade, as the latter has been shown pre-clinically to augment mobilization of HSCs when combined with a CXCR4 inhibitor, GPC-100 (Sukhtankar et al... These studies support further investigation of whether simultaneous blockade of CXCR4 and ADBR2 may potentiate chemotherapy response in AML by limiting microenvironment mediated chemotherapy protection and reveal that patients with new diagnosis may be more susceptible to this approach."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ADRB2 • CD123 • CD34 • CXCL12 • CXCR4 • FLT3 • IL3RA • NPM1 • PTPRC

Combined CXCR-4 Inhibition with Novel Agent GPC-100 (burixafor) and Beta 2 Adrenergic Receptor Blockade Enhances Cytarabine Response for Acute Myeloid Leukemia Blasts on Stroma (ASH 2024) - P1 | "The CXCR4 inhibitor plerixafor improves yields of mobilized normal hematopoietic stem cells (HSCs) in combination with filgrastim (G-CSF). Clinical trials of CXCR4 inhibitors have been conducted to mobilize AML out of the protected BM niche, including plerixafor with 7+3 or MEC, BL-8040 with cytarabine (araC), LY2510924 with idarubicin/araC, and ulocuplumab (human IgG4 antibody) with MEC...In addition, high throughput drug screening of AML on stroma, but not in suspension or on CXCL12 coated plates, revealed that combination of the CXCR4 inhibitor GPC-100 and beta blocker propranolol, with araC, increased drug sensitivity (reduced IC50 by ≥4 to >10 fold) as compared to araC alone for AML cells on HS-5 human stromal cell line or autologous patient mesenchymal stromal cells...Conclusions : These studies support further investigation of whether simultaneous blockade of CXCR4 and ADRB2 may potentiate chemotherapy response in AML, perhaps by disrupting..."

Stroma • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ADRB2 • CD58 • CXCL12 • CXCR4 • FLT3 • NPM1 • TP53

Diagnosis and Management of Waldenstrom's Macroglobulinemia (ICML 2025) - P2 | "New or emerging options for patients progressing on c-BTKi include pirtobrutinib, BGB-16673, venetoclax, and sonrotoclax...CXCR4 antagonists such as plerixafor or ulocuplumab can sensitize CXCR4Mut-expressing WM cells to ibrutinib [22-24]...6 BTK Mutations BTKCys481 is the binding site for covalent BTK inhibitors (cBTK-i), including ibrutinib, zanubrutinib, acalabrutinib, orelabrutinib and tirabrutinib...For symptomatic treatment-naïve patients, chemoimmunotherapy with bendamustine and rituximab (Benda-R), dexamethasone, rituximab, and cyclophosphamide (DRC), as well as cBTK-i can be considered...Additional options in second or later relapse include re-use of chemotherapy if a response lasted for > 3 years, alternative chemoimmunotherapy, nucleoside analogs, or everolimus [38]...Zanubrutinib in combination with ixazomib and dexamethasone (ZID) is being investigated in a study in China (NCT04463953) and has shown high levels of response activity and good..."

IO biomarker • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia • BCLAF1 • CXCL12 • FOXO3 • IL10 • IL6 • IRAK4 • MYD88 • PLCG2 • SYK • TNFAIP3 • TRAF3IP2

Molecular targets of neuroplasticity in ischemic stroke: insights from GEO database, single-cell analysis and immune infiltration analysis. (PubMed, Front Aging Neurosci) - "Finally, the Leronlimab, Ulocuplumab, Burixafor, and MSX-122 are promising drugs to treat IS via targeting on CCR5 and CXCR4. In conclusion, our findings suggest that CCR5 and CXCR4 are promising targets for enhancing neuroplasticity post-ischemic stroke, thus providing potentially effective and reliable therapeutic targets for future interventional strategy."

Journal • Cardiovascular • Ischemic stroke • CD8 • CXCR4 • GRM1 • TIMP1

“CXCR4-ADRB2 simultaneous inhibition therapy, clinical trial success rate↑” GPCRL announces innovative treatment for blood cancer [Google translation] (BioTimes) - "In addition, the research team conducted a retrospective study on the previously conducted phase 2 clinical trial of Ulocuplumab, a CXCR4 inhibitor, and confirmed that the clinical efficacy CR/CRi significantly improved to 76.9% (8 out of 13 patients) in the patient group taking non-selective beta-blockers that inhibit ADRB2. In contrast, the CR/CRi of patients who did not take beta-blockers was only 37.5% (18 out of 48 patients)."

Retrospective data • Acute Myelogenous Leukemia

CXCR4 as a therapeutic target in acute myeloid leukemia. (PubMed, Leukemia) - "Additionally, we explore clinical implications, including prognosis, correlation with WBC count, blast count in the bone marrow and peripheral blood, as well as its association with FLT3-ITD, NPM1 mutations, and FAB classification. Finally, this paper extensively discusses drugs that specifically target the CXCL12-CXCR4 axis, including plerixafor/AMD3100, ulocuplumab, peptide E5, and motixafortide, shedding light on their potential therapeutic value in the treatment of AML."

Journal • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CXCL12 • CXCR4 • FLT3 • NPM1

Investigational CXCR4 inhibitors in early phase development for the treatment of hematological malignancies. (PubMed, Expert Opin Investig Drugs) - "In light of these discoveries, scientific investigations and clinical trials have underscored the therapeutic promise found in small-molecule antagonists like plerixafor, peptides/peptidomimetics such as BKT140, monoclonal antibodies like PF-06747143 and ulocuplumab, as well as microRNAs. The information collectively emphasizes the potential of CXCR4 antagonists as a therapeutic strategy for hematologic malignancies, showcasing advancements in preclinical and clinical studies. As these therapeutic strategies progress through clinical trials, their potential to reshape the prognosis of hematologic malignancies will become increasingly apparent."

Journal • Review • Hematological Disorders • Hematological Malignancies • Oncology • CXCL12 • CXCR4

A Study of Ulocuplumab And Ibrutinib in Symptomatic Patients With Mutated CXCR4 Waldenstrom's Macroglobulinemia (clinicaltrials.gov) - P1 | N=13 | Terminated | Sponsor: Dana-Farber Cancer Institute | Phase classification: P1/2 ➔ P1 | Active, not recruiting ➔ Terminated; Sponsor decision to end follow-up early

Phase classification • Trial termination • Hematological Disorders • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Non-Hodgkin’s Lymphoma • Waldenstrom Macroglobulinemia • CA6 • CXCR4 • MYD88

Research progress of the chemokine/chemokine receptor axes in the oncobiology of multiple myeloma (MM). (PubMed, Cell Commun Signal) - "Utilizing anti-tumor chemokines or blocking pro-tumor chemokines may provide new therapeutic strategies for managing MM. Inspired by developed CXCR4 antagonists, including plerixafor, ulocuplumab, and motixafortide, more small molecular antagonists or antibodies for pro-tumor chemokine ligands and their receptors can be developed and used in clinical practice. Along with inhibiting pro-tumor chemokines, studies suggest combining chemokines with chimeric antigen receptor (CAR)-T therapy is promising and efficient."

Biomarker • Journal • Review • Hematological Malignancies • Multiple Myeloma • Oncology • CCL19 • CCL2 • CCL3 • CXCL10 • CXCL12 • CXCL13 • CXCL8 • PPBP

CXCR4 Blockade Targets Progression of Primary T Cell Acute Lymphoblastic Leukemia (ASH 2022) - "D) Schematic of treatment with aCXCR4 Ab (MDX-1338) or isotype control. E-F) Kaplan-Meier survival graph (left) and peripheral blood levels of hCD45+ of NSG mice engrafted with primary adult (E) and pediatric (F) T-ALL samples and treated with aCXCR4 Ab or isotype control."

Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • ANXA5 • CXCL12 • CXCR4 • NOTCH1 • PTPRC

An Investigational Immuno-therapy Study of Ulocuplumab in Combination With Low Dose Cytarabine in Patients With Newly Diagnosed Acute Myeloid Leukemia (clinicaltrialsregister.eu) - P1/2 | N=157 | Completed | Sponsor: Bristol-Myers Squibb International Corporation

Combination therapy • New P1/2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Targeted Therapies and Emerging Novel Treatment Approaches for Waldenström Macroglobulinemia. (PubMed, Clin Lymphoma Myeloma Leuk) - "Standard treatment regimens combine the anti-CD20 antibody rituximab with alkylating agents (eg, bendamustine, cyclophosphamide), nucleoside analogs (eg, fludarabine, cladribine), or proteasome inhibitors (eg, bortezomib, carfilzomib, and ixazomib). Covalent BTK inhibitors (eg, ibrutinib, acalabrutinib, zanubrutinib) have shown to be safe and highly effective in patients with WM. Novel and promising agents in this disease include next-generation covalent BTK inhibitors (eg, tirabrutinib, orelabrutinib), non-covalent BTK inhibitors (eg, pirtobrutinib, ARQ531), BCL-2 antagonists (eg, venetoclax), and CXCR4-targeted agents (eg, mavorixafor, ulocuplumab), among others. Future studies will focus on developing fixed-duration combinations regimens with these novel agents aimed at increasing durable responses while minimizing toxicity and cost."

IO biomarker • Journal • Hematological Disorders • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia • BCL2 • CXCR4 • MYD88

The contributory roles of the CXCL12/CXCR4/CXCR7 axis in normal and malignant hematopoiesis: A possible therapeutic target in hematologic malignancies. (PubMed, Eur J Pharmacol) - "Plerixafor, BKT140, LY2510924, PF-06747143, ulocuplumab, and NOX-A12 are among the most well-known CXCR4 and CXCL12 modulators that their therapeutic efficacies have been evaluated in different pre-clinical and clinical studies of hematologic malignancies. To have an overview of the importance of CXCL12/CXCR4 and CXCL12/CXCR7 axes in the pathogenesis of leukemia and to gather information about the latest advances as well as challenges in targeting these axes in clinical settings, the present review has begun with a discussion about how aberrant expression of CXCL12/CXCR4 and CXCL12/CXCR7 pathways might regulate leukemogenesis and ended by outlining the key news of preclinical and clinical investigations in leukemia treatment."

Journal • Review • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • ACKR3 • CXCL12 • CXCR4

"Phase 1 study of ibrutinib and the CXCR4 antagonist ulocuplumab in CXCR4-mutated Waldenström macroglobulinemia https://t.co/fUeEG8utAR" (,@BloodJournal)

Hematological Disorders • Lymphoma • Lymphoplasmacytic Lymphoma • Waldenstrom Macroglobulinemia

A Phase Ib/II Study of the Novel Anti-CXCR4 Antibody Ulocuplumab (BMS-936564) in Combination with Lenalidomide Plus Low-Dose Dexamethasone, or with Bortezomib Plus Dexamethasone in Subjects with Relapsed or Refractory Multiple Myeloma (ASH 2018) - "Ulocuplumab was given weekly in combination with either 25mg lenalidomide on days 1-21 and 40mg oral dexamethasone on days 1, 8, 15, and 22 of the 28-day cycles on Arm A or 1.3 mg/m2 bortezomib on days 1, 4, 8, and 11 and 20mg oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12 of the 21-day cycles on Arm B since cycle 2. Conclusion : This study shows that the blockade of the CXCR4-CXCL12 axis by Ulocuplumab is safe and has an encouraging response rate of over 50% in the Len-Dex arm of patients with relapsed/refractory myeloma. The distinct mechanisms of action of this antibody, as well as its non- cross resistance with currently approved approaches, make it a new class of anti-myeloma drug that warrants further exploration and evaluation in future clinical trials."

Clinical • Combination therapy • P1/2 data • Biosimilar • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Neutropenia • Oncology

Phase I study of Ibrutinib and the CXCR4 antagonist Ulocuplumab in CXCR4 mutated Waldenstrom Macroglobulinemia. (PubMed, Blood) - P1/2 | "The study demonstrates the feasibility of combining a CXCR4-antagonist with ibrutinib, and provides support for the development of CXCR4-antagonists for CXCR4Mut WM. www.clinicaltrials.gov (NCT03225716)."

Journal • P1 data • Dermatology • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Lymphoplasmacytic Lymphoma • Thrombocytopenia • Waldenstrom Macroglobulinemia • MYD88

A Study of Ulocuplumab And Ibrutinib in Symptomatic Patients With Mutated CXCR4 Waldenstrom's Macroglobulinemia (clinicaltrials.gov) - P1/2; N=13; Active, not recruiting; Sponsor: Dana-Farber Cancer Institute; Trial primary completion date: Jan 2021 ➔ Jan 2023

Clinical • Trial primary completion date • Hematological Disorders • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Non-Hodgkin’s Lymphoma • Waldenstrom Macroglobulinemia • CXCR4 • MYD88

Management of Waldenström macroglobulinemia in 2020. (PubMed, Hematology Am Soc Hematol Educ Program) - "Alkylating agents (bendamustine, cyclophosphamide), proteasome inhibitors (bortezomib, carfilzomib, ixazomib), anti-CD20 monoclonal antibodies (rituximab, ofatumumab), and Bruton tyrosine kinase (BTK) inhibitors (ibrutinib, acalabrutinib, zanubrutinib) are safe and highly effective treatment options in patients with WM. Because novel covalent and noncovalent BTK inhibitors (tirabrutinib, vecabrutinib, LOXO-305, ARQ-531), BCL2 antagonists (venetoclax), and CXCR4-targeting agents (ulocuplumab, mavorixafor) are undergoing clinical development in WM, the future of WM therapy certainly appears bright and hopeful."

IO biomarker • Journal • Hematological Disorders • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia

At the bedside: Profiling and treating patients with CXCR4-expressing cancers. (PubMed, J Leukoc Biol) - "To date, Sanofi Genzyme's plerixafor is the only marketed CXCR4 inhibitor (i.e., Food and Drug Administration-approved in 2008 for stem cell mobilization)...These small molecules, peptides, and Abs include balixafortide (POL6326, Polyphor), mavorixafor (X4P-001, X4 Pharmaceuticals), motixafortide (BL-8040, BioLineRx), LY2510924 (Eli Lilly), and ulocuplumab (Bristol-Myers Squibb)...Biol. xx: xx-xx; 2020."

Clinical • Journal • Review • Oncology • Solid Tumor

Anti-CXCR4 Antibody Combined With Activated and Expanded Natural Killer Cells for Sarcoma Immunotherapy. (PubMed, Front Immunol) - "Moreover, in assays in vitro, anti-CXCR4 blocking antibody (MDX1338) efficiently reduced migration and invasion of alveolar rhabdomyosarcoma RH30 cells...In this study, we propose a novel therapeutic approach based on anti-CXCR4 blocking antibody in combination with NKAE cell therapy to prevent rhabdomyosarcoma tumor implantation and lung metastasis. These results provide the first evidence for the efficacy of this combined immunotherapy for preventing sarcoma disease dissemination."

IO Biomarker • Journal • Lung Cancer • Oncology • Pediatrics • Rhabdomyosarcoma • Sarcoma • Solid Tumor

A Phase Ib/II Trial of the First-in-Class Anti-CXCR4 Antibody Ulocuplumab in Combination with Lenalidomide or Bortezomib plus Dexamethasone in Relapsed Multiple Myeloma. (PubMed, Clin Cancer Res) - "This study showed that blockade of the CXCR4-CXCL12 axis by ulocuplumab is safe with acceptable adverse events and leads to a high response rate in combinationwith lenalidomide and dexamethasone in patients with relapsed/refractory myeloma, making CXCR4-inhibitors a promising class of anti-myeloma drugs that should be further explored in clinical trials."

Combination therapy • Journal • P1/2 data • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia

[VIRTUAL] Waldenström Macroglobulinemia – 2020 Update on Management and Future Directions (SOHO 2020) - "Combinations of bortezomib-rituximab +/– dexamethasone have been associated with major (≥ partial response) response rates (MRR) of 57–83%, while carfilzomib-rituximab-dexamethasone has shown an MRR of 68%, and ixazomib-rituximab-dexamethasone, an MRR of 50%.8, 9, 10, 11 By comparison, alkylating agent-based regimens (R-CHOP, R-CVP, ritxumab-cyclophosphamide-dexamethasone, rituximab-bendamustine) have shown MRRs of 77–96%. Of these, rituximab-bendamustine is the preferred regimen in light of improved progression-free survival compared with R-CHOP and superior toxicity profile.12, 13 Rituximab monotherapy is generally a sub-optimal choice for patients needing systemic therapy, with overall response rates (minor + partial response) of 20–50%, and short progression-free survival (12–24 months).14 For patients whose WM exhibits the MYDL265PCXCR4WT gene mutation profile, ibrutinib, with or without rituximab, may also be considered frontline, due to its high MRR (92%) and..."

IO Biomarker • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD38 • CXCR4 • MYD88

What is new in the treatment of Waldenstrom macroglobulinemia? (PubMed, Leukemia) - "The approval of the oral Bruton tyrosine kinase (BTK) inhibitor ibrutinib alone and in combination with rituximab has expanded the treatment options for WM patients. The present Perspective would focus on exciting treatment strategies under development for WM patients, such as proteasome inhibitors (e.g., ixazomib), BTK inhibitors (e.g., acalabrutinib, zanubrutinib, vecabrutinib), BCL2 inhibitors (e.g., venetoclax), and anti-CXCR4 antibodies (e.g., ulocuplumab), among others. It is certainly an exciting time for WM therapy development with novel and promising treatment options in the horizon."

IO Biomarker • Journal • Review • Gene Therapies • Hematological Disorders • Hematological Malignancies • Lymphoma • Monoclonal Gammopathy • Non-Hodgkin’s Lymphoma • Oncology • Pain