Slideset on: Jakubowiak AJ, Benson DM, Bensinger W, et al. Phase I trial of anti-CS1 monoclonal antibody elotuzumab in combination with bortezomib in the.

Slides:

Advertisements

Similar presentations

Brown JR et al. Proc ASH 2013;Abstract 523.

Advertisements

Phase 1/2 Study of Weekly MLN9708, an Investigational Oral Proteasome Inhibitor, in Combination with Lenalidomide and Dexamethasone in Patients with Previously.

Efficacy and Safety of Three Bortezomib-Based Combinations in Elderly, Newly Diagnosed Multiple Myeloma Patients: Results from All Randomized Patients.

Novel AKT Inhibitor Afuresertib in Combination with Bortezomib and Dexamethasone Demonstrates Favorable Safety Profile and Significant Clinical Activity.

Richardson PG et al. Proc ASH 2013;Abstract 535.

Palumbo A et al. Proc ASH 2012;Abstract 446.

Carfilzomib: High Single-Agent Response Rate with Minimal Neuropathy Even in High-Risk Patients 1 Baseline Peripheral Neuropathy Does Not Impact the Efficacy.

Lesokhin AM et al. Proc ASH 2014;Abstract 291.

Results of a Phase II Trial of Brentuximab Vedotin as First Line Salvage Therapy in Relapsed/Refractory HL Prior to AHCT Chen RW et al. Proc ASH 2014;Abstract.

1 Baz R et al. Proc ASH 2014;Abstract Lacy MQ et al.

Single-Agent Lenalidomide in Patients with Relapsed/Refractory Mantle Cell Lymphoma Following Bortezomib: Efficacy, Safety and Pharmacokinetics from the.

SAR650984, a CD38 Monoclonal Antibody in Patients with Selected CD38+ Hematological Malignancies — Data from a Dose-Escalation Phase I Study Martin TG.

Treatment with Bendamustine- Bortezomib-Dexamethasone in Relapsed/Refractory Multiple Myeloma Shows Significant Activity and Is Well Tolerated Ludwig H.

Phase II Clinical and Correlative Study of Carfilzomib, Lenalidomide, and Dexamethasone Followed by Lenalidomide Extended Dosing (CRD-R) Induces High Rates.

Weekly MLN9708, an Investigational Oral Proteasome Inhibitor, in Relapsed/Refractory Multiple Myeloma: Results from a Phase I Study After Full Enrollment.

A Phase 2 Study of Elotuzumab in Combination with Lenalidomide and Low-Dose Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: Updated.

A Phase Ib Dose Escalation Trial of SAR (Anti-CD-38 mAb) in Combination with Lenalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma.

Palumbo A et al. Proc ASH 2014;Abstract 175.

A Phase II Study with Carfilzomib, Cyclophosphamide and Dexamethasone (CCd) for Newly Diagnosed Multiple Myeloma Bringhen S et al. Proc ASH 2013;Abstract.

Ibrutinib, Single Agent or in Combination with Dexamethasone, in Patients with Relapsed or Relapsed/Refractory Multiple Myeloma (MM): Preliminary Phase.

Ruan J et al. Proc ASH 2013;Abstract 247.

Lenalidomide Is Safe and Active in Waldenstrom Macroglobulinemia (WM) 1 Updated Results from a Multicenter, Open-Label, Dose-Escalation Phase 1b/2 Study.

A Phase 3 Study Evaluating the Efficacy and Safety of Lenalidomide Combined with Melphalan and Prednisone Followed by Continuous Lenalidomide Maintenance.

A Phase 2 Study of Elotuzumab in Combination with Lenalidomide and Low-Dose Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma Lonial.

Maintenance Therapy with Bortezomib plus Thalidomide (VT) or Bortezomib plus Prednisone (VP) in Elderly Myeloma Patients Included in the GEM2005MAS65 Spanish.

Brentuximab Vedotin Administered Concurrently with Multi-Agent Chemotherapy as Frontline Treatment of ALCL and Other CD30-Positive Mature T-Cell and NK-Cell.

ClaPD (Clarithromycin, Pomalidomide, Dexamethasone) Therapy in Relapsed or Refractory Multiple Myeloma Mark TM et al. Proc ASH 2012;Abstract 77.

A Phase 3 Prospective, Randomized, International Study (MMY-3021) Comparing Subcutaneous and Intravenous Administration of Bortezomib in Patients with.

Low Dose Decitabine Versus Best Supportive Care in Elderly Patients with Intermediate or High Risk MDS Not Eligible for Intensive Chemotherapy: Final Results.

A Multi-Center Phase I/II Trial of Carfilzomib and Pomalidomide with Dexamethasone (Car-Pom-d) in Patients with Relapsed/Refractory Multiple Myeloma Shah.

Phase II Multicenter Study of Single-Agent Lenalidomide in Subjects with Mantle Cell Lymphoma Who Relapsed or Progressed After or Were Refractory to Bortezomib:

VANTAGE 095: An International, Multicenter, Open-Label Study of Vorinostat (MK-0683) in Combination with Bortezomib in Patients with Relapsed or Refractory.

Brentuximab Vedotin in Combination with RCHOP as Front-Line Therapy in Patients with DLBCL: Interim Results from a Phase 2 Study Yasenchak CA et al. Proc.

MM-005: A Phase 1, Multicenter, Open-Label, Dose-Escalation Study to Determine the Maximum Tolerated Dose for the Combination of Pomalidomide, Bortezomib,

Slideset on: Jakubowiak AJ, Dytfeld D, Griffith KA, et al. A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone.

Phase II Study: Pembrolizumab + Pomalidomide/Dexamethasone for Patients With R/R MM New Findings in Hematology: Independent Conference Coverage* of ASH.

Final Results for the 1703 Phase 1b/2 Study of Elotuzumab in Combination with Lenalidomide and Dexamethasone in Patients with Relapsed/Refractory Multiple.

New Findings in Hematology: Independent Conference Coverage* of ASH 2015, December 5-8, 2015, Orlando, Florida ARRAY : Phase II Trial of Carfilzomib.

KEYNOTE-021: Pembrolizumab + Ipilimumab Active in Previously Treated Advanced NSCLC CCO Independent Conference Highlights of the 2015 ASCO Annual Meeting*

Pomalidomide + Low-Dose Dexamethasone (POM + LoDex) vs High-Dose Dexamethasone (HiDex) in Relapsed/Refractory Multiple Myeloma (RRMM): MM-003 Analysis.

CCO Independent Conference Highlights

Phase II SAKK 35/10 Trial: Rituximab Plus Lenalidomide Shows Durable Activity in Untreated Follicular Lymphoma New Findings in Hematology: Independent.

: Mogamulizumab in R/R Adult T-Cell Leukemia-Lymphoma

Campos M et al. Proc EHA 2013;Abstract B2009.

R1.이용석 / modulator pf.한재준.

Moskowitz CH et al. Proc ASH 2015;Abstract 182.

Campos M et al. Proc EHA 2013;Abstract B2009.

ELOQUENT-2: Elotuzumab + Len/Dex in R/R MM

Reeder CB et al. ASCO 2009; Abstract (Poster)

Korde N et al. Proc ASH 2012;Abstract 732.

Pomalidomide Plus Low-Dose Dex vs High-Dose Dex in Rel/Ref Myeloma

ELOQUENT-2: Addition of Elotuzumab to Len/Dex Extends PFS in Relapsed/Refractory Myeloma CCO Independent Conference Highlights of the 2015 ASCO Annual.

Randomized, Open-Label Phase 1/2 Study of Pomalidomide Alone or in Combination with Low-Dose Dexamethasone in Patients with Relapsed and Refractory Multiple.

Phase III EMN02/HO95 MM Trial: Upfront ASCT Prolongs PFS vs Bortezomib, Melphalan, Prednisone in Newly Diagnosed MM CCO Independent Conference Coverage*

KEYNOTE-023: Pembrolizumab + Lenalidomide + Dexamethasone Shows Promising Activity and Safety in R/R MM CCO Independent Conference Coverage* of the 2016.

Phase Ib MMY1001: Daratumumab Plus Pom/Dex for Patients With R/R MM

Multiple Myeloma in Session 2015: An Online Journal Club for Hematology/Oncology Fellows This program is supported by educational grants from Celgene Corporation.

Elotuzumab, Lenalidomide, and Low-Dose Dexamethasone in Relapsed/Refractory Myeloma Slideset on: Lonial S, Vij R, Harousseau JL, et al. Elotuzumab in combination.

San Miguel JF et al. 1 Proc EHA 2013;Abstract S1151.

Dimopoulos MA et al. Proc ASH 2012;Abstract LBA-6.

Pharmacy Perspectives in Multiple Myeloma: Relapsed and/or Refractory Disease.

Fowler NH et al. Proc ASCO 2010;Abstract 8036.

Jakubowiak AJ et al. Proc ASH 2010;Abstract 862.

Ansell SM et al. Proc ASH 2012;Abstract 798.

Final Results of a Frontline Phase 1/2 Study of Carfilzomib, Lenalidomide, and Low-Dose Dexamethasone (CRd) in Multiple Myeloma (MM)1 Final Results from.

Multiple Myeloma Overview all transplants, autologous and allogeneic (period ) N=28.887

Forero-Torres A et al. Proc ASH 2011;Abstract 3711.

Pomalidomide plus Low-Dose Dexamethasone in Myeloma Refractory to Both Bortezomib and Lenalidomide: Comparison of Two Dosing Strategies in Dual-Refractory.

Advani RH et al. Proc ASH 2011;Abstract 443.

Presentation transcript:

Slideset on: Jakubowiak AJ, Benson DM, Bensinger W, et al. Phase I trial of anti-CS1 monoclonal antibody elotuzumab in combination with bortezomib in the treatment of relapsed/ refractory multiple myeloma. J Clin Oncol 2012;30: Elotuzumab and Bortezomib Combination Active, Safe in Relapsed/Refractory Multiple Myeloma This program is supported by educational grants from

clinicaloptions.com/oncology An Online Journal Club Resource for Physician Fellows  Elotuzumab [1,2] –Anti-CS1, humanized IgG1 –Elotuzumab binding to myeloma cells blocks adhesion to bone marrow stroma –Proposed mechanism is by NK-dependent ADCC  CS1 cell surface antigen [1,2] –High expression on MM cells, normal plasma cells –Low to no expression on normal cells –Intermediate expression on NK cells Elotuzumab Background 1. Hsi ED, et al. Clin Cancer Res. 2008;14: Tai YT, et al. Blood. 2008;112:

clinicaloptions.com/oncology An Online Journal Club Resource for Physician Fellows Phase I Study Design  Criteria –Active disease, 1-3 previous therapies –No recent SCT, ≥ grade 2 neuropathy  Treatment (21-day cycle) –Bortezomib 1.3 mg/m 2 IV on Days 1, 4, 8, 11 –Elotuzumab at 1 of 4 escalating doses: 2.5, 5, 10, or 20 mg/kg IV on Days 1 and 11 –Given within 30 min of bortezomib  Primary objective: MTD –Secondary objectives: efficacy, safety, PD/PK Jakubowiak AJ, et al. J Clin Oncol. 2012;30:

clinicaloptions.com/oncology An Online Journal Club Resource for Physician Fellows  MTD not reached at 20 mg/kg (maximum planned dose) Patients (%) N = 28  Adverse events typically resolved spontaneously  Hypersensitivity in 1 patient Grade 3/4 toxicity Jakubowiak AJ, et al. J Clin Oncol. 2012;30: Elotuzumab/Bortezomib MTD and Safety Lymphopenia Fatigue Neutropenia Thrombocytopenia Peripheral neuropathy Hyperglycemia

clinicaloptions.com/oncology An Online Journal Club Resource for Physician Fellows  ORR: 48% (13 of 27 evaluable patients) −67% in bortezomib-refractory disease (2 of 3 patients) −43% in lenalidomide-refractory disease (3 of 7 patients) −70% in high-risk cytogenetics (7 of 10 patients) −Response rates higher with fewer previous MM therapies  PD/PK −CS1 targets saturated to median 95% at 20 mg/kg −Peak elotuzumab serum levels ≥ 100 µg/mL at each dose −Elotuzumab serum trough levels, CS1 saturation not affected by added coadministration of bortezomib Jakubowiak AJ, et al. J Clin Oncol. 2012;30: Elotuzumab/Bortezomib Efficacy and PD/PK

clinicaloptions.com/oncology An Online Journal Club Resource for Physician Fellows Elotuzumab/Bortezomib Summary  MTD not reached at 20 mg/kg  48% ORR –Includes responses seen in bortezomib- and lenalidomide- refractory patients  CS1 targets saturated to median 95% at 20 mg/kg  Data suggest CS1 may be potentially useful target in multiple myeloma Jakubowiak AJ, et al. J Clin Oncol. 2012;30: