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|Ref Type||Journal Article|
|Authors||Ghobrial IM, Liu CJ, Redd RA, Perez RP, Baz R, Zavidij O, Sklavenitis-Pistofidis R, Richardson PG, Anderson KC, Laubach J, Henrick P, Savell A, Reyes K, Hornburg K, Chuma S, Sabbatini P, Robbins MD, Becker PS|
|Title||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.|
|Journal||Clinical cancer research : an official journal of the American Association for Cancer Research|
|Date||2020 Jan 15|
|Abstract Text||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.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Ulocuplumab||BMS-936564|MDX1338||CXCR4 Inhibitor 15||Ulocuplumab (BMS-936564) is a monoclonal antibody that binds to CXCR4 and prevents binding of SDF-1 (CXCL12), potentially resulting in increased apoptosis and decreased migration of tumor cells (PMID: 23213054, PMID: 31672767).|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||multiple myeloma||not applicable||Bortezomib + Dexamethasone + Ulocuplumab||Phase I||Actionable||In a Phase I trial, Ulocuplumab (BMS-936564) in combination with Velcade (bortezomib) and Adexone (dexamethasone) demonstrated safety and preliminary efficacy, resulted in an overall response rate of 25.0% (4/16) and a clinical benefit rate of 50% (8/16) in patients with relapsed multiple myeloma (PMID: 31672767).||31672767|
|Unknown unknown||multiple myeloma||not applicable||Dexamethasone + Lenalidomide + Ulocuplumab||Phase I||Actionable||In a Phase I trial, Ulocuplumab (BMS-936564) in combination with Revlimid (lenalidomide) and Adexone (dexamethasone) demonstrated safety and preliminary efficacy, resulted in an overall response rate of 55.2% (16/29) and a clinical benefit rate of 72.4% (21/29) in patients with relapsed multiple myeloma (PMID: 31672767).||31672767|