AstraZeneca : Calquence data to show improved progression-free

Calquence data to show improved progression-free

Released : 06.11.2019

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-termefficacy, safety and tolerability data on Calquence in relapsed or refractory CLL from the Phase I/II ACE-CL- 001 trial
• First-timedata 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	Obinutuzumab
	obinutuzumab		monotherapy	plus chlorambucil
	N = 179		N = 179	N = 177
Stratified analysis, median follow-up 28 months
Hazard ratio for PFS	HR 0.10	HR 0.20	n/a
endpoint (vs.	(primary endpoint)	(secondary
obinutuzumab +			endpoint)
chlorambucil),
stratified analysis	95% CI 0.06-0.17,	95% CI 0.13-0.30,
	P<0.0001	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.	E L E V A T E T N : P h a s e 3 S t u d y o f	Oral Presentation
	A c a l a b r u t i n i b C o m b i n e d w i t h	Saturday 7 December
	Obinutuzumab (O) or Alone vs O Plus	07:30 ET
	Chlorambucil (Clb) in Patients (Pts) With	Orange County C o n v e n t i o n
	Treatment-Naive Chronic Lymphocytic	Center, Hall D
	Leukemia (CLL)
Lampson, BL.	Preliminary Safety and Efficacy Results	Oral Presentation
	from a Phase 2 Study of Acalabrutinib,	Saturday 7 December
	V e n e t o c l a x a n d O b i n u t u z u m a b i n	07:45 ET
	P a t i e n t s w i t h P r e v i o u s l y U n t r e a t e d	Orange County C o n v e n t i o n
	Chronic Lymphocytic Leukemia (CLL)	Center, Hall D
Frei, CR.	Treatment Patterns and Outcomes of	Oral Presentation
	1205 Patients on Novel Agents in the US	Monday 9 December
	Veterans Health Administration (VHA)	15:15 ET
	System: Results from Retrospective	Orange County C o n v e n t i o n
	EMR and Chart Review Study in the	Center, Valencia A (W415A)
	Real-World Setting
Goyal, RK.	Overall Survival, Adverse Events, and	Oral Presentation
	Economic Burden in Medicare Patients	Monday 9 December
	with Chronic Lymphocytic Leukemia	15:15 ET
	Receiving Cancer-Directed Therapy	Orange County C o n v e n t i o n
		Center, Valencia A (W415A)
Furman, RR.	Acalabrutinib Monotherapy in Patients	Poster Presentation
	w i t h R e l a p s e d / R e f r a c t o r y C h r o n i c	Sunday 8 December
	L y m p h o c y t i c L e u k e m i a : 4 2 - M o n t h	18:00 - 20:00 ET
	Follow-Up of a Phase 2 Study	Orange County C o n v e n t i o n
		Center, Hall B
Brown, JR.	A Phase 3 Trial Comparing the Efficacy	Poster Presentation
	a n d S a f e t y o f A c a l a b r u t i n i b i n	Monday 9 December
	Combination with Venetoclax with or	18:00 - 20:00 ET

	without Obinutuzumab, Compared with	Orange County C o n v e n t i o n
	I n v e s t i g a t o r ' s	C h o i c e o f	Center, Hall B
	Chemoimmunotherapy in Patients with
	P r e v i o u s l y U n t r e a t e d C h r o n i c
	Lymphocytic Leukemia (CLL) without
	del(17p) or TP53 Mutation
Mantle cell lymphoma
Kabadi, S.	Overall Survival, Adverse Events, and	Oral Presentation
	Economic Burden in Medicare-Insured	Saturday 7 December
	Patients with Mantle Cell Lymphoma	08:00 ET
	Receiving Cancer-Directed Therapy	Orange County C o n v e n t i o n
			Center, W308
Ryan, K.	Characteristics of Mantle Cell Lymphoma
	( M C L ) a n d C h r o n i c L y m p h o c y t i c	Poster Presentation
	Leukemia (CLL) Patients Treated with	Sunday 8 December
	Acalabrutinib in a Real World Setting in	18:00 - 20:00 ET
	the United States		Orange County C o n v e n t i o n
			Center, Hall B
Acute myeloid leukaemia
Zeidan, A.	Efficacy and Safety of Azacitidine (AZA)	Oral Presentation
	in Combination with the Anti - PD - L1	Monday 9 December
	Durvalumab (durva) for the Front-line	16:30 ET
	Treatment of Older Patients (pts) with	Orange County C o n v e n t i o n
	Acute Myeloid Leukemia (AML) Who Are	Center, Chapin Theater (W320)
	Unfit for Intensive Chemotherapy (IC)
	and Pts with Higher-Risk Myelodysplastic
	Syndromes (HR-MDS): Results from a
	Large, International, Randomized Phase
	2 Study
Donnellan, W.	A Phase I/II Study of AZD2811NP as	Poster Presentation
	M o n o t h e r a p y o r i n C o m b i n a t i o n i n	Monday 9 December
	T r e a t m e n t - N a ï v e o r R / R A M L / M D S	18:00 - 20:00 ET
	P a t i e n t s N o t E l i g i b l e f o r I n t e n s i v e	Orange County C o n v e n t i o n
	Induction Therapy		Center, Hall B
Diffuse large B-cell lymphoma
Roschewski,	P R I S M : A P l a t f o r m P r o t o c o l f o r t h e	Poster Presentation
M.	T r e a t m e n t o f R e l a p s e d / R e f r a c t o r y	Sunday 8 December
	Aggressive Non-Hodgkin Lymphoma	18:00 - 20:00 ET
			Orange County C o n v e n t i o n
			Center, Hall B
Moskowitz,	Safety and Antitumor Activity Study of
CH.	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 with	Saturday 7 December
	b o r t e z o m i b a n d i n h i b i t o r s t o D N A	17:30 - 19:30 ET
	damage response in multiple myeloma	Orange County C o n v e n t i o n
			Center, Hall B
Sacco, A.	Specific targeting of KRAS using a novel	Poster Presentation
	h i g h - a f f i n i t y K R A S a n t i s e n s e	Sunday 8 December
	oligonucleotide in myeloma.	18:00 - 20:00 ET
			Orange County C o n v e n t i o n
			Center, Hall B
Xing, L.	MEDI2228, a novel BCMA antibody-PBD	Poster Presentation
	conjugate, sensitizes human multiple	Sunday 8 December
	m y e l o m a c e l l s t o N K c e l l - m e d i a t e d	18:00 - 20:00 ET
	c y t o t o x i c i t y a n d u p r e g u l a t e s C D 3 8	Orange County C o n v e n t i o n
	e x p r e s s i o n i n M M	c e l l s : c l i n i c a l	Center, Hall B
	implication
Primary MDS-induced anaemia
Henry, D.	R o x a d u s t a t ( F G 4 5 9 2 ; A S P 1 5 1 7 ;	Oral Presentation
	AZD9941) in the Treatment of Anemia in	Monday 9 December
	Patients with Lower Risk Myelodysplastic	16:30 - 18:00 ET
	S y n d r o m e ( L R - M D S ) a n d L o w R e d	Orange County C o n v e n t i o n
	Blood Cell (RBC) Transfusion Burden	Center, W311ABCD
	(LTB)

About ELEVATE-TN

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-mindedscience-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.coma n d f o l l o w t h e C o m p a n y o n Twitter @AstraZeneca.

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References

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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