Full results from Phase III ELEVATE TN trial showed 93% of patients on CALQUENCE combined with obinutuzumab vs. 47% of patients on chlorambucil plus obinutuzumab remained free of disease progression or death at 24 months

Trial also showed 87% of patients on CALQUENCE alone remained free of disease progression or death at 24 months

WILMINGTON, DE, USA I December 07, 2019 I AstraZeneca today presented results from the interim analysis of the Phase III ELEVATE TN trial, showing that CALQUENCE® (acalabrutinib) combined with obinutuzumab or as monotherapy significantly improved progression-free survival (PFS) compared to chlorambucil plus obinutuzumab, a standard chemo-immunotherapy treatment, in patients with previously untreated chronic lymphocytic leukemia (CLL).

The Independent Review Committee (IRC)-assessed results were presented at the 2019 American Society of Hematology Annual Meeting and Exhibition in Orlando, US. At a median follow-up of 28.3 months, CALQUENCE in combination with obinutuzumab or as a monotherapy significantly reduced the risk of disease progression or death by 90% and 80%, respectively, vs. chlorambucil plus obinutuzumab.

In an exploratory analysis, CALQUENCE in combination or alone demonstrated consistent PFS improvements across most pre-specified subgroups of patients with high-risk disease characteristics, including the unmutated immunoglobulin heavy-chain variable gene (IGHV), del(11q) and complex karyotype. Overall, the safety and tolerability profile of CALQUENCE observed in the ELEVATE TN trial was consistent with its known profile.

José Baselga, Executive Vice President, Oncology R&D said: “On the heels of approvals in the US, Australia and Canada, these full results provide further evidence that CALQUENCE, as a new treatment option for patients with chronic lymphocytic leukemia, demonstrates remarkable efficacy and a favorable tolerability profile. These results also provide, for the first time, post-hoc analysis data exploring the potential progression-free survival benefit of adding obinutuzumab to a BTK inhibitor versus BTK inhibitor monotherapy in a randomized trial.”

Dr. Jeff Sharman, Director of Research at Willamette Valley Cancer Institute, Medical Director of Hematology Research for The US Oncology Network, and a lead author of the ELEVATE TN trial, said: “In the detailed results from the ELEVATE TN trial comparing CALQUENCE to a commonly used chemo-immunotherapy treatment regimen, CALQUENCE demonstrated a clinically meaningful improvement in progression-free survival, while maintaining its known tolerability and safety profile. These are encouraging results for a patient population that is known to face multiple comorbidities, and where tolerability is a critical factor in their treatment.”

Summary of key efficacy results as assessed by IRC from the ELEVATE TN trial at median follow-up of 28.3 months:

       
Efficacy measure

CALQUENCE plus
obinutuzumab

N = 179

CALQUENCE
monotherapy
N = 179
Chlorambucil plus
obinutuzumab
N = 177
PFS
Number of events (%) 14 (7.8) 26 (14.5) 93 (52.5)
Median (95% CI), months NR
(NE, NE)
NR
(34.2, NE)
22.6
(20.2, 27.6)
HR (95% CI) 0.10 (0.06, 0.17) 0.20 (0.13, 0.30)
p-value <0.0001 <0.0001
Estimated PFS at 24 months, % 93  87  47 
ORR
ORR, n (%)
(95% CI)
168 (93.9)
(89.3, 96.5)
153 (85.5)
(79.6, 89.9)
139 (78.5)
(71.9, 83.9)
p-value <0.0001 =0.0763
OS
Number of events (%) 9 (5.0) 11 (6.1) 17 (9.6)
Median (95% CI), months NR (NE, NE) NR (NE, NE) NR (NE, NE)
HR (95% CI) 0.47 (0.21, 1.06) 0.60 (0.28, 1.27)
p-value =0.0577 =0.1556
CI, Confidence Interval; NR, Not Reached; NE, Not Evaluable; HR, Hazard Ratio; ORR, Overall Response Rate, OS, Overall Survival

Adverse events (AEs) led to treatment discontinuation in 11.2% of patients treated with CALQUENCE in combination with obinutuzumab and 8.9% of patients treated with CALQUENCE monotherapy versus 14.1% of patients treated with chlorambucil plus obinutuzumab.

With over two years of follow-up, 79% of patients in both the CALQUENCE-containing arms remain on CALQUENCE as a monotherapy. In the CALQUENCE combination arm (n=178), the most common AEs of any grade (≥30%) included headache (39.9%), diarrhea (38.8%) and neutropenia (31.5%). In the CALQUENCE monotherapy arm (n=179), the most common AEs of any grade (≥30%) included headache (36.9%) and diarrhea (34.6%). In the chlorambucil plus obinutuzumab arm (n=169), the most common AEs of any grade (≥30%) included neutropenia (45.0%), infusion-related reaction (39.6%) and nausea (31.4%).

       
Other AEs of clinical interest (%)1 CALQUENCE plus
obinutuzumab
N = 178
CALQUENCE
monotherapy
N = 179
Chlorambucil plus
obinutuzumab
N = 169
Any Grade ≥3 Any Grade ≥3 Any Grade ≥3
Atrial fibrillation 3.4% 0.6% 3.9% 0% 0.6% 0%
Major bleeding 2.8% 1.7% 1.7% 1.7% 1.2% 0%
Hypertension 7.3% 2.8% 4.5% 2.2% 3.6% 3.0%
Infection 69.1% 20.8% 65.4% 14.0% 43.8% 8.3%
SPM excluding NMSC 5.6% 3.4% 2.8% 1.1% 1.8% 1.2%
SPM, secondary primary malignancy; NMSC, non-melanoma skin cancer

These findings, along with previously reported data from the Phase III ASCEND trial in relapsed or refractory CLL, support the recent approvals of CALQUENCE by the US FDA and the Australian Therapeutic Goods Administration for the treatment of adult patients with CLL or small lymphocytic lymphoma (SLL) and by Health Canada for CLL.

INDICATION AND USAGE

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 trials.

CALQUENCE is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

About CALQUENCE

In the US and Australia, CALQUENCE® (acalabrutinib) is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) and in Canada for CLL. In the US, Canada, Australia, Brazil, Qatar, the United Arab Emirates, Mexico, Argentina, Singapore, Chile, and recently India, CALQUENCE is also approved for adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. CALQUENCE was approved for MCL under accelerated review in the US, continued approval for previously treated MCL is contingent upon verification and confirmation of clinical benefit in confirmatory trials.

CALQUENCE is a next-generation selective inhibitor of Bruton’s tyrosine kinase (BTK). It binds covalently to BTK, thereby inhibiting its activity. In B-cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion.

As part of an extensive clinical development program, AstraZeneca and Acerta Pharma are currently evaluating CALQUENCE in 23 company-sponsored clinical trials. CALQUENCE is being developed for the treatment of multiple B-cell blood cancers including CLL, MCL, diffuse large B-cell lymphoma, Waldenstrom macroglobulinemia, follicular lymphoma and other hematologic malignancies. Several Phase III clinical trials in CLL are ongoing, including ASCEND, ELEVATE-TN, ELEVATE-RR (ACE-CL-006) evaluating CALQUENCE vs. ibrutinib in patients with previously-treated high-risk CLL, and ACE-CL-311 evaluating CALQUENCE in combination with venetoclax and with/without obinutuzumab vs. chemoimmunotherapy in patients with previously untreated CLL without 17p deletion or TP53 mutation.

About ELEVATE-TN

ELEVATE-TN (ACE-CL-007) is a randomized, multicenter, 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. Patients 65 years of age or older, between 18 and 65 years of age with a total Cumulative Illness Rating Scale (CIRS) >6 or creatinine clearance of 30 to 69 mL/min were enrolled. In the trial, 535 patients were randomized (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 approximately every 12 hours until disease progression or unacceptable toxicity) in combination with obinutuzumab. Patients in the third arm received CALQUENCE monotherapy (100mg approximately every 12 hours until disease progression or unacceptable toxicity).

The primary endpoint is 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.

About CLL

Chronic lymphocytic leukemia (CLL) is one of the most common types of leukemia in adults, with an estimated 105,000 new cases globally in 2016 and 20,720 new cases in the US in 2019, and the number of people living with CLL is expected to grow with improved treatment as patients live longer with disease. In CLL, too many blood stem cells in the bone marrow become abnormal lymphocytes and these abnormal cells have difficulty fighting infections.7 As the number of abnormal cells grows there is less room for healthy white blood cells, red blood cells and platelets. This could result in anemia, infection and bleeding. B-cell receptor signaling through BTK is one of the essential growth pathways for CLL.

About AstraZeneca in hematology

Leveraging its strength in oncology, AstraZeneca has established hematology as one of four key oncology disease areas of focus. The Company’s hematology franchise includes two US FDA-approved medicines and a robust global development program for a broad portfolio of potential blood cancer treatments. Acerta Pharma serves as AstraZeneca’s hematology 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 a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to AstraZeneca’s main capabilities, the Company is actively pursuing innovative partnerships and investments that accelerate the delivery of our strategy as illustrated by our investment in Acerta Pharma in hematology.

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

About AstraZeneca

AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas – Oncology, Cardiovascular, Renal & Metabolism and Respiratory. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit www.astrazeneca-us.com and follow the Company on Twitter @AstraZenecaUS.

SOURCE: AstraZeneca