RNS Number : 5205S

AstraZeneca PLC

06 November 2019

6 November 2019 14:00 GMT

Calquence data to show improved progression-free survival in Phase III front-line chronic lymphocytic leukaemia trial at ASH 2019 Annual Meeting

Robust early-stage pipeline advancements and presentations across

multiple scientific platforms demonstrate potential to improve

treatment outcomes in blood cancers with high unmet need

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 leukaemia (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.(1)

The Company will present over 30 abstracts, including seven oral presentations, in CLL, mantle cell lymphoma (MCL), acute myeloid leukaemia (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 anaemia in patients with primary myelodysplastic syndrome (MDS)

Dave Fredrickson, Executive Vice President, Oncology Business Unit said: "AstraZeneca continues to demonstrate its strength in haematology, 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 leukaemia."

Key headline data from the Calquence Phase III ELEVATE-TN trial

 Efficacy measure         Calquence plus      Calquence monotherapy      Obinutuzumab 
                            obinutuzumab             N = 179           plus chlorambucil 
                              N = 179                                       N = 177 
 Stratified analysis, median follow-up 28 months 
 Hazard ratio                 HR 0.10                HR 0.20                  n/a 
  for PFS endpoint       (primary endpoint)    (secondary endpoint) 
  (vs. obinutuzumab 
  + chlorambucil),                              95% CI 0.13-0.30, 
  stratified analysis    95% CI 0.06-0.17,           p<0.0001 
                                                median not reached 
                         median not reached                            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 11% 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 a 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 of 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 anaemia 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.(2)

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

 Sharman, J.    ELEVATE TN: Phase 3 Study                      Oral Presentation 
                 of Acalabrutinib Combined                      Saturday 7 December 
                 with Obinutuzumab (O) or Alone                 07:30 ET 
                 vs O Plus Chlorambucil (Clb)                   Orange County Convention 
                 in Patients (Pts) With Treatment-Naive         Center, Hall D 
                 Chronic Lymphocytic Leukemia 
               =============================================  ============================ 
 Lampson, BL.   Preliminary Safety and Efficacy                Oral Presentation 
                 Results from a Phase 2 Study                   Saturday 7 December 
                 of Acalabrutinib, Venetoclax                   07:45 ET 
                 and Obinutuzumab in Patients                   Orange County Convention 
                 with Previously Untreated                      Center, Hall D 
                 Chronic Lymphocytic Leukemia 
               =============================================  ============================ 
 Frei, CR.      Treatment Patterns and Outcomes                Oral Presentation 
                 of 1205 Patients on Novel                      Monday 9 December 
                 Agents in the US Veterans                      15:15 ET 
                 Health Administration (VHA)                    Orange County Convention 
                 System: Results from Retrospective             Center, Valencia A (W415A) 
                 EMR and Chart Review Study 
                 in the Real-World Setting 
               =============================================  ============================ 
 Goyal, RK.     Overall Survival, Adverse                      Oral Presentation 
                 Events, and Economic Burden                    Monday 9 December 
                 in Medicare Patients with                      15:15 ET 
                 Chronic Lymphocytic Leukemia                   Orange County Convention 
                 Receiving Cancer-Directed                      Center, Valencia A (W415A) 
               =============================================  ============================ 
 Furman, RR.    Acalabrutinib Monotherapy                      Poster Presentation 
                 in Patients with Relapsed/Refractory           Sunday 8 December 
                 Chronic Lymphocytic Leukemia:                  18:00 - 20:00 ET 
                 42-Month Follow-Up of a Phase                  Orange County Convention 
                 2 Study                                        Center, Hall B 
               =============================================  ============================ 
 Brown, JR.     A Phase 3 Trial Comparing                      Poster Presentation 
                 the Efficacy and Safety of                     Monday 9 December 
                 Acalabrutinib in Combination                   18:00 - 20:00 ET 
                 with Venetoclax with or without                Orange County Convention 
                 Obinutuzumab, Compared with                    Center, Hall B 
                 Investigator's Choice of Chemoimmunotherapy 
                 in Patients with Previously 
                 Untreated Chronic Lymphocytic 
                 Leukemia (CLL) without del(17p) 
                 or TP53 Mutation 
               =============================================  ============================ 
 Mantle cell lymphoma 
 Kabadi, S.     Overall Survival, Adverse                      Oral Presentation 
                 Events, and Economic Burden                    Saturday 7 December 
                 in Medicare-Insured Patients                   08:00 ET 
                 with Mantle Cell Lymphoma                      Orange County Convention 
                 Receiving Cancer-Directed                      Center, W308 
 Ryan, K.       Characteristics of Mantle                       Poster Presentation 
                 Cell Lymphoma (MCL) and Chronic                 Sunday 8 December 
                 Lymphocytic Leukemia (CLL)                      18:00 - 20:00 ET 
                 Patients Treated with Acalabrutinib             Orange County Convention 
                 in a Real World Setting in                      Center, Hall B 
                 the United States 
               =============================================  ============================ 
 Acute myeloid leukaemia 
 Zeidan, A.     Efficacy and Safety of Azacitidine             Oral Presentation 
                 (AZA) in Combination with                      Monday 9 December 
                 the Anti-PD-L1 Durvalumab                      16:30 ET 
                 (durva) for the Front-line                     Orange County Convention 
                 Treatment of Older Patients                    Center, Chapin Theater 
                 (pts) with Acute Myeloid Leukemia              (W320) 
                 (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 
               =============================================  ============================ 
 Donnellan,     A Phase I/II Study of AZD2811NP                Poster Presentation 
  W.             as Monotherapy or in Combination               Monday 9 December 
                 in Treatment-Naïve or                     18:00 - 20:00 ET 
                 R/R AML/MDS Patients Not Eligible              Orange County Convention 
                 for Intensive Induction Therapy                Center, Hall B 
               =============================================  ============================ 
 Diffuse large B-cell lymphoma 
 Roschewski,    PRISM: A Platform Protocol                     Poster Presentation 
  M.             for the Treatment of Relapsed/Refractory       Sunday 8 December 
                 Aggressive Non-Hodgkin Lymphoma                18:00 - 20:00 ET 
                                                                Orange County Convention 
                                                                Center, Hall B 
               =============================================  ============================ 
 Moskowitz,     Safety and Antitumor Activity 
  CH.            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                 Poster Presentation 
                 drug resistance and synergizes                 Saturday 7 December 
                 with bortezomib and inhibitors                 17:30 - 19:30 ET 
                 to DNA damage response in                      Orange County Convention 
                 multiple myeloma                               Center, Hall B 
               =============================================  ============================ 
 Sacco, A.      Specific targeting of KRAS                     Poster Presentation 
                 using a novel high-affinity                    Sunday 8 December 
                 KRAS antisense oligonucleotide                 18:00 - 20:00 ET 
                 in myeloma.                                    Orange County Convention 
                                                                Center, Hall B 
               =============================================  ============================ 
 Xing, L.       MEDI2228, a novel BCMA antibody-PBD            Poster Presentation 
                 conjugate, sensitizes human                    Sunday 8 December 
                 multiple myeloma cells to                      18:00 - 20:00 ET 
                 NK cell-mediated cytotoxicity                  Orange County Convention 
                 and upregulates CD38 expression                Center, Hall B 
                 in MM cells: clinical implication 
               =============================================  ============================ 
 Primary MDS-induced anaemia 
 Henry, D.      Roxadustat (FG4592; ASP1517;                   Oral Presentation 
                 AZD9941) in the Treatment                      Monday 9 December 
                 of Anemia in Patients with                     16:30 - 18:00 ET 
                 Lower Risk Myelodysplastic                     Orange County Convention 
                 Syndrome (LR-MDS) and Low                      Center, W311ABCD 
                 Red Blood Cell (RBC) Transfusion 
                 Burden (LTB) 


ELEVATE-TN (ACE-CL-007) is a randomised, multicentre, open-label Phase III trial evaluating the safety and efficacy of Calquence in combination with obinutuzumab, a CD20 monoclonal antibody, or Calquence alone vs. chlorambucil, a chemotherapy, in combination with obinutuzumab in previously untreated patients with CLL. In the trial, 535 patients were randomised (1:1:1) into three arms. Patients in the first arm received chlorambucil in combination with obinutuzumab. Patients in the second arm received Calquence (100mg twice daily until disease progression or unacceptable toxicity) in combination with obinutuzumab. Patients in the third arm received Calquence monotherapy (100mg twice daily until disease progression or unacceptable toxicity).(3)

The primary endpoint is progression-free survival (PFS) in the Calquence and obinutuzumab arm compared to the chlorambucil and obinutuzumab arm, assessed by an independent review committee (IRC), and a key secondary endpoint is IRC-assessed PFS in the Calquence monotherapy arm compared to the chlorambucil and obinutuzumab arm. Other secondary endpoints include objective response rate, time to next treatment and overall survival.(3)

About AstraZeneca in Haematology

Leveraging its strength in oncology, AstraZeneca has established haematology as one of four key oncology disease areas of focus. The Company's haematology franchise includes two US FDA-approved medicines and a robust global development programme for a broad portfolio of potential blood cancer treatments. Acerta Pharma serves as AstraZeneca's haematology research and development arm. AstraZeneca partners with like-minded science-led companies to advance the discovery and development of therapies to address unmet need.

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of

new medicines that has the potential to transform patients' lives and the Company's future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline

of small molecules and biologics in development, we are committed to advance Oncology as one of AstraZeneca's four Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by the investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms - Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates - and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal and Metabolism, and Respiratory. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.

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1. Barf T, et al. Acalabrutinib (ACP-196): A Covalent Bruton Tyrosine Kinase Inhibitor with a Differentiated Selectivity and In Vivo Potency Profile. J Pharmacol Exp Ther. 2017;363 (2) 240-252. Available online. Accessed October 2019.

2. American Cancer Society. What Are Myelodysplastic Syndromes? Available online. Accessed October 2019.

3. ClinicalTrials.gov. Elevate CLL TN: Study of Obinutuzumab + Chlorambucil, Acalabrutinib (ACP-196) + Obinutuzumab, and Acalabrutinib in Subjects With Previously Untreated CLL. NCT02475681. Available online. Accessed October 2019.

Adrian Kemp

Company Secretary

AstraZeneca PLC

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November 06, 2019 09:10 ET (14:10 GMT)