AstraZeneca Highlights Will Present First Data From Phase 3 ELEVATE-TN Trial Assessing CALQUENCE In Patients with Previously-Untreated Chronic Lymphocytic Leukemia At ASH Dec. 7-10, 2019

AstraZeneca will present the first data from the Phase III ELEVATE-TN trial assessing CALQUENCE® (acalabrutinib), a next-generation selective Bruton’s tyrosine kinase (BTK) inhibitor, in patients with

Benzinga · 11/06/2019 20:18

AstraZeneca will present the first data from the Phase III ELEVATE-TN trial assessing CALQUENCE® (acalabrutinib), a next-generation selective Bruton’s tyrosine kinase (BTK) inhibitor, in patients with previously untreated chronic lymphocytic leukemia (CLL), as well as data from novel-combination trials across multiple blood cancers at the 2019 American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, USA, December 7-10. 

The Company will present over 30 abstracts, including seven oral presentations, in CLL, mantle cell lymphoma (MCL), acute myeloid leukemia (AML), diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (MM). Key data include: 

The first presentation of data from the pivotal Phase III ELEVATE-TN trial evaluating CALQUENCE in combination with obinutuzumab and CALQUENCE monotherapy versus obinutuzumab combined with chlorambucil chemotherapy in previously untreated CLL 
Long-term efficacy, safety and tolerability data on CALQUENCE in relapsed or refractory CLL from the Phase I/II ACE-CL-001 trial 
First-time data on roxadustat as a potential new treatment for anemia in patients with primary myelodysplastic syndromes (MDS) 
Dave Fredrickson, Executive Vice President, Oncology Business Unit said: “AstraZeneca continues to demonstrate its strength in hematology, presenting new research at ASH that spans targeted therapies across eight blood cancers. This year we are especially excited to present the ELEVATE-TN data demonstrating the impressive efficacy and tolerability of CALQUENCE in 1st-line chronic lymphocytic leukemia.” 

        
Key headline data from the CALQUENCE Phase III ELEVATE-TN trial 
 
        
Efficacy measure 
  CALQUENCE plus 

obinutuzumab 

N = 179 
  CALQUENCE 

monotherapy 

N = 179 
  Obinutuzumab 

plus chlorambucil 

N = 177 
 
Stratified analysis, median follow-up 28 months 
 
Hazard ratio for PFS endpoint (vs. obinutuzumab + chlorambucil), stratified analysis 
  HR 0.10 
(primary endpoint) 

95% CI 0.06–0.17, 

p<0.0001 

median not reached 
   
 HR 0.20 
(secondary endpoint) 

95% CI 0.13–0.30, 

p<0.0001 

median not reached 
   
 n/a 

median 22.6 months 
 
        

Select adverse events (AEs) include infusion reactions, which were less frequent with CALQUENCE plus obinutuzumab (13%) than with obinutuzumab plus chlorambucil (40%). Additionally, AEs led to treatment discontinuation in 12% of patients on CALQUENCE plus obinutuzumab, 9% of patients on CALQUENCE, and 14% of patients on obinutuzumab plus chlorambucil. With >2 y of follow-up, 79% of patients in both the CALQUENCE-containing arms remain on CALQUENCE as monotherapy. Other select AEs (CALQUENCE plus obinutuzumab or CALQUENCE vs chlorambucil plus obinutuzumab) included atrial fibrillation (any grade: 3% or 4% vs. 1%), bleeding (any grade/Grade =3: 43%/2% or 39%/2% vs. 12%/0%), and hypertension (Grade =3: 3% or 2% vs. 3%). 

Full data from the ELEVATE-TN trial will be presented at ASH by the primary investigators. AstraZeneca has submitted CALQUENCE for US regulatory review in 1st-line and relapsed/refractory CLL. 

Raising the bar for CLL treatment outcomes with CALQUENCE 
In addition to the oral presentation on the ELEVATE-TN results, key presentations include: 

An oral presentation on preliminary data from a Phase II investigator-initiated trial evaluating CALQUENCE combined with obinutuzumab and venetoclax in patients with previously untreated CLL, including high-risk disease status and a trial-in-progress poster detailing an ongoing Phase III trial to evaluate this novel combination in patients with previously untreated CLL without del(17p) or TP53 mutation. 
Long-term (42-month) follow-up results from the Phase I/II ACE-CL-001 trial confirming CALQUENCE initial efficacy from this trial for the treatment of relapsed or refractory CLL and providing additional data on duration of response and long-term tolerability. 
Exploring a potential treatment option for a challenging comorbidity in blood cancer 

An oral presentation on first-time data from a global Phase III trial evaluating roxadustat to treat anemia in patients with primary MDS. Considered a type of cancer, MDS is a group of diverse bone marrow disorders in which the bone marrow does not produce enough healthy blood cells. Approximately one in three MDS patients can progress to AML. 
Exploring potential new medicines from the pipeline and new treatment strategies for aggressive or treatment-resistant blood cancers 

In AML, an oral presentation and four poster presentations, including results from an IMFINZI® (durvalumab) and azacitidine combination for the 1st-line treatment of older, chemotherapy-ineligible patients and data from a Phase I/II clinical trial of AZD2811(nanoparticles), as a monotherapy or in combination with azacitidine in previously untreated or relapsed/refractory patients who are not eligible for intensive induction therapy. 
In DLBCL, five abstracts, including a poster presentation detailing the ongoing Phase I PRISM trial of CALQUENCE in four different combinations with potential new medicines targeting STAT3, ATR, CD47 and BRD4. 
In MM, three poster presentations, including results of a Phase I trial of MEDI2228, a BCMA antibody-PBD conjugate and potential new medicine, as a monotherapy and in combinations with bortezomib and DNA damage response medicines and results from an in vitro trial of AZD4785 alone or with proteasome inhibitors targeting mutant KRAS. 
  
Key AstraZeneca presentations at ASH 2019 
 
 
Lead author 
  Abstract title 
  Presentation details 
 
Chronic lymphocytic leukemia 
 
Sharman, J. 
  ELEVATE-TN: Phase 3 Study of Acalabrutinib Combined with Obinutuzumab (O) or Alone vs O Plus Chlorambucil (Clb) in Patients (Pts) With Treatment-Naive Chronic Lymphocytic Leukemia (CLL) 
  Oral Presentation 

Saturday 7 December 

07:30 ET 

Orange County Convention Center, Hall D 
 
Lampson, BL. 
  Preliminary Safety and Efficacy Results from a Phase 2 Study of Acalabrutinib, Venetoclax and Obinutuzumab in Patients with Previously Untreated Chronic Lymphocytic Leukemia (CLL) 
  Oral Presentation 

Saturday 7 December 

07:45 ET 

Orange County Convention Center, Hall D 
 
Frei, CR. 
  Treatment Patterns and Outcomes of 1205 Patients on Novel Agents in the US Veterans Health Administration (VHA) System: Results from the Largest Retrospective EMR and Chart Review Study in the Real-World Setting 
  Oral Presentation 

Monday 9 December 

15:15 ET 

Orange County Convention Center, Valencia A (W415A) 
 
Goyal, RK. 
  Overall Survival, Adverse Events, and Economic Burden in Medicare Patients with Chronic Lymphocytic Leukemia Receiving Cancer-Directed Therapy 
  Oral Presentation 

Monday 9 December 

15:15 ET 

Orange County Convention Center, Valencia A (W415A) 

  
 
Furman, RR. 
  Acalabrutinib monotherapy in patients with relapsed/refractory chronic lymphocytic leukemia: long-term follow-up of a phase 2 study 
  Poster Presentation 

Sunday 8 December 

18:00 to 20:00 ET 

Orange County Convention Center, Hall B 
 
Brown, JR. 
  A Phase 3 Trial Comparing the Efficacy and Safety of Acalabrutinib in Combination with Venetoclax with or without Obinutuzumab, Compared with Investigator’s Choice of Chemoimmunotherapy in Patients with Previously Untreated Chronic Lymphocytic Leukemia (CLL) without del(17p) or TP53 Mutation 
  Poster Presentation 

Monday 9 December 

18:00 to 20:00 ET 

Orange County Convention Center, Hall B 
 
Mantle cell lymphoma 
 
Kabadi, S. 
  Overall Survival, Adverse Events, and Economic Burden in Medicare Patients with Mantle Cell Lymphoma Receiving Cancer-Directed Therapy 
  Oral Presentation 

Saturday 7 December 

08:00 ET 

Orange County Convention Center, W308 
 
Ryan, K. 
  Characteristics of Mantle Cell Lymphoma (MCL) and Chronic Lymphocytic Leukemia (CLL) Patients Treated with Acalabrutinib in a Real World Setting in the United States 
  Poster Presentation 

Sunday 8 December 

18:00 to 20:00 ET 

Orange County Convention Center, Hall B 
 
Acute myeloid leukemia 
 
Zeidan, A. 
  Efficacy and Safety of Azacitidine (AZA) in Combination with the Anti-PD-L1 Durvalumab (durva) for the Front-line Treatment of Older Patients (pts) with Acute Myeloid Leukemia (AML) Who Are Unfit for Intensive Chemotherapy (IC) and Pts with Higher-Risk Myelodysplastic Syndromes (HR-MDS): Results from a Large, International, Randomized Phase 2 Study 
  Oral Presentation 

Monday 9 December 

16:30 ET 

Orange County Convention Center, Chapin Theater (W320) 
 
Donnellan, W. 
  A Phase I/II study of AZD2811NP as monotherapy or in combination in treatment-naïve or R/R AML/MDS patients not eligible for intensive induction therapy 
  Poster Presentation 

Monday 9 December 

18:00 to 20:00 ET 

Orange County Convention Center, Hall B 
 
Diffuse large B-cell lymphoma 
 
Roschewski, M. 
  A platform protocol for the treatment of relapsed/refractory aggressive Non-Hodgkin’s Lymphoma 
  Poster Presentation 

Sunday 8 December 

18:00 to 20:00 ET 

Orange County Convention Center, Hall B 
 
Moskowitz, CH. 
  Safety and Antitumor Activity Study of Loncastuximab Tesirine and Durvalumab in Diffuse Large B-Cell, Mantle Cell, or Follicular Lymphoma 
    
 
Multiple myeloma 
 
Xing, L. 
  Anti-BCMA PBD MEDI2228 combats drug resistance and synergizes with bortezomib and inhibitors to DNA damage response in multiple myeloma: further therapeutic implication 
  Poster Presentation 

Saturday 7 December 

17:30 to 19:30 ET 

Orange County Convention Center, Hall B 
 
Sacco, A. 
  Specific targeting of KRAS using a novel high-affinity KRAS antisense oligonucleotide in myeloma 
  Poster Presentation 

Sunday 8 December 

18:00 to 20:00 ET 

Orange County Convention Center, Hall B 
 
Xing, L. 
  MEDI2228, a novel BCMA antibody-PBD conjugate, sensitizes human multiple myeloma cells to NK cell-mediated cytotoxicity and upregulates CD38 expression in MM cells: further clinical implication 
  Poster Presentation 

Sunday 8 December 

18:00 to 20:00 ET 

Orange County Convention Center, Hall B 
 
Primary MDS-induced anemia 
 
Henry, D. 
  Roxadustat (FG4592; ASP1517; AZD9941) in the Treatment of Anemia in Patients with Lower Risk Myelodysplastic Syndrome (LR-MDS) and Low Red Blood Cell (RBC) Transfusion Burden (LTB) 
  Oral Presentation 

Monday 9 December 

16:30 to 18:00 ET 

Orange County Convention Center, W311ABCD 
 
      

Indication and Usage for CALQUENCE® (acalabrutinib) 
CALQUENCE is a Bruton tyrosine kinase (BTK) inhibitor indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. 

This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial.