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

• Published in: Clinical cancer research Vol. 26; no. 2; pp. 344 - 353
• Main Authors: Ghobrial, Irene M., Liu, Chia-Jen, Redd, Robert A., Perez, Raymond P., Baz, Rachid, Zavidij, Oksana, Sklavenitis-Pistofidis, Romanos, Richardson, Paul G., Anderson, Kenneth C., Laubach, Jacob, Henrick, Patrick, Savell, Alexandra, Reyes, Kaitlen, Hornburg, Kalvis, Chuma, Stacey, Sabbatini, Peter, Robbins, Michael D., Becker, Pamela S.
• Format: Journal Article
• Language: English
• Published: United States 15.01.2020
• Subjects: Aged; Antibodies, Monoclonal, Humanized - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bortezomib - administration & dosage; Dexamethasone - administration & dosage; Humans; Lenalidomide - administration & dosage; Maximum Tolerated Dose; Middle Aged; Multiple Myeloma - drug therapy; Multiple Myeloma - pathology; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - pathology; Patient Safety; Receptors, CXCR4 - antagonists & inhibitors; Receptors, CXCR4 - immunology; Survival Rate; Treatment Outcome
• ISSN: 1078-0432; 1557-3265; 1557-3265
• DOI: 10.1158/1078-0432.CCR-19-0647

Ulocuplumab (BMS-936564) is a first-in-class fully human IgG4 monoclonal anti-CXCR4 antibody that inhibits the binding of CXCR4 to CXCL12. This phase Ib/II study aimed to determine the safety and tolerability of ulocuplumab alone and in combination with lenalidomide and dexamethasone (Arm A), or bortezomib and dexamethasone (Arm B), in patients with relapsed/refractory multiple myeloma. Forty-six patients were evaluated (median age, 60 years; range, 53-67). The median number of prior therapies was 3 (range, 1-11), with 70% of subjects having received ≥3. This trial had a dose-escalation and a dose-expansion part. Using a 3+3 design on both arms of the trial, ulocuplumab's dose was escalated to a maximum of 10 mg/kg without reaching MTD. The most common treatment-related adverse events (AE) were neutropenia (13 patients, 43.3%) in Arm A and thrombocytopenia (6 patients, 37.5%) in Arm B. No deaths related to study drugs occurred. The combination of ulocuplumab with lenalidomide and dexamethasone showed a high response rate (PR or better) of 55.2% and a clinical benefit rate of 72.4%, even in patients who had been previously treated with immunomodulatory agents (IMiD). This study showed that blockade of the CXCR4-CXCL12 axis by ulocuplumab is safe with acceptable AEs and leads to a high response rate in combination with lenalidomide and dexamethasone in patients with relapsed/refractory myeloma, making CXCR4 inhibitors a promising class of antimyeloma drugs that should be further explored in clinical trials.