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CALQUENCE Significantly Prolonged the Time Patients Lived Without Disease Progression or Death in Previously Untreated Chronic Lymphocytic Leukemia

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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

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).

IMPORTANT SAFETY INFORMATION ABOUT CALQUENCE® (acalabrutinib) capsules

Serious and Opportunistic Infections

Fatal and serious infections, including opportunistic infections, have occurred in patients with hematologic malignancies treated with CALQUENCE.

Serious or Grade 3 or higher infections (bacterial, viral, or fungal) occurred in 19% of 1029 patients exposed to CALQUENCE in clinical trials, most often due to respiratory tract infections (11% of all patients, including pneu

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