AstraZeneca aims to transform the oncology treatment landscape with diverse early pipeline and novel combinations at AACR

28 March 2022 07:05 BST
(Updated 30 March 2022)
 

Clinical data in immuno-oncology and DNA damage response illustrate potential of next-wave medicines to advance cancer care

First data for novel molecules show promising anti-cancer activity and showcase strategy to attack cancer from multiple angles
 

AstraZeneca will present new data underscoring the breadth of the Company’s early oncology portfolio at the American Association for Cancer Research (AACR) Annual Meeting in New Orleans, 8 to 13 April 2022.

Data from 60 presentations, including 5 oral and 3 mini-oral presentations, will feature the Company’s next wave of potential cancer medicines spanning its immuno-oncology (IO), DNA Damage Response (DDR) and Antibody Drug Conjugate (ADC) scientific platforms. This includes key data shared from three potential new medicines that illustrate the Company’s innovative approach to designing molecules that address key challenges in treating cancer, including the ability to target different, complementary mechanisms.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “We are serious about leading a revolution in oncology, which is why we continue to pioneer new ways to target cancer earlier and with greater precision, for the benefit of patients. Our data at AACR from next-wave Immuno-Oncology medicines, PARP inhibitors and antibody drug conjugates demonstrate the potential of our diverse portfolio and reflect our vision to target cancer from every angle."

Introducing the next wave of IO therapies
The first clinical results will be shared for MEDI5752, a novel bispecific antibody, that simultaneously targets the immune checkpoint proteins PD-1 and CTLA-4, in solid tumours. Bispecific antibodies are a promising IO approach that combines the potential benefits of two medicines in one. MEDI5752 was engineered to achieve combined blockade of CTLA-4 and PD-1, to improve the therapeutic index when compared to targeting these proteins using two separate medicines.

A presentation from the NeoCOAST randomised Phase II trial in resectable, early-stage non-small cell lung cancer will highlight improved disease responses with novel Imfinzi (durvalumab) combinations including with oleclumab, an anti-CD73 monoclonal antibody, and with monalizumab1, an anti-NKG2A checkpoint inhibitor, when compared to Imfinzi alone.

Additionally, four presentations will describe novel molecules targeting interleukin-12 (IL-12) and leukaemia inhibitor factor (LIF) and illustrate the potential of targeting non-redundant mechanisms to modulate the immune tumour microenvironment.

Building the next generation of PARP inhibitors
The first data will be presented from the PETRA Phase I clinical trial investigating AZD5305, a next-generation PARP1-selective inhibitor, in patients with tumours harbouring specific homologous recombination repair gene mutations. AZD5305 is designed to selectively target PARP1, killing cancer cells by targeting tumour cell DNA damage repair mechanisms. This approach could allow PARP inhibitors to expand into new settings and offer new opportunities for combinations with DNA damage pathway activating agents such as ADCs. Preclinical data will be presented that support this hypothesis showing the activity of Enhertu (trastuzumab deruxtecan) in combination with DDR agents including PARP1-selective inhibitors. AstraZeneca is collaborating with Daiichi Sankyo Company, Limited (Daiichi Sankyo) to develop and commercialise Enhertu globally.

Additionally, four presentations will describe the discovery of AZD9574, a novel PARP1 selective inhibitor designed to cross the blood brain barrier to enable the targeting of primary and secondary brain malignancies.

Innovative approaches to deliver a next-wave ADC
The first preclinical data will be shared on AZD8205, a novel ADC targeting B7-H4, a protein overexpressed in a range of solid tumours. This molecule is the first ADC to incorporate AstraZeneca’s proprietary linker technology, demonstrating the Company’s progress in establishing in-house ADC expertise and building leadership in this field.


Key AstraZeneca presentations during AACR 2022

Presenting author

Abstract title

Presentation details

IO

Tran, B

MEDI5752, a novel PD-1/CTLA-4 bispecific checkpoint inhibitor for advanced solid tumors: First-in-human study

Abstract #CT016

Oral

Session CTPL04 - Combination Immunotherapy Clinical Trials

12 April 2022

11:46 – 12:01 CDT

Cascone, T

NeoCOAST-2: a randomized, open-label, phase 2 study of neoadjuvant durvalumab plus novel immunotherapies and chemotherapy (CT) followed by adjuvant durvalumab plus novel agents, in patients with resectable non-small-cell lung cancer (NSCLC)

Abstract #CT124 / 6

Poster – Trial in progress (TiP)

Session PO.CT02.03 - Phase II Trials in Progress

11 April 2022

09:00 – 12:30 CDT

Cascone, T

NeoCOAST: open-label, randomized, phase 2, multidrug platform study of neoadjuvant durvalumab alone or combined with novel agents in patients (pts) with resectable, early-stage non-small-cell lung cancer (NSCLC)

Abstract #CT011

Oral

Session CTPL03 - Neoadjuvant and Perioperative Immunotherapy Clinical Trials

11 April 2022

11:16 – 11:31 CDT

Shrestha, P

Durvalumab (D) + platinum-etoposide (EP) in 1L extensive-stage small-cell lung cancer (ES-SCLC): Exploratory analysis of SCLC molecular subtypes in CASPIAN

Abstract #CT024

Mini-oral

Session CTMS01 - Biomarker Advances in Clinical Trials

10 April 2022

15:50 – 160:00 CDT

Reinmuth, N

 

Durvalumab (D) plus tremelimumab (T) in platinum-refractory/resistant extensive-stage small cell lung cancer (ES-SCLC): Efficacy, safety and ctDNA dynamics from Arm A of the phase 2 BALTIC study

 

Abstract #CT533

Poster – Clinical Trial

Session OPO.CT02.01 - Phase II Clinical Trials

8 April 2022

12:00 – 13:00 CDT

 

Fayette, J

INTERLINK-1: A phase 3, randomized, double-blind, placebo-controlled, multicenter, global study of monalizumab in combination with cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma previously treated with an immune checkpoint inhibitor

Abstract #CT236 / 7

Poster – TiP

Session PO.CT03.02 - Phase III Trials in Progress

12 April 2022

13:30 – 17:00 CDT

Carneiro, BA

First-in-human study of MEDI1191 (mRNA encoding IL-12) plus durvalumab in patients (pts) with advanced solid tumors

Abstract #CT183 / 8

Poster – Clinical Trial

Session PO.CT01.02 - Phase I Clinical Trials 2

12 April 2022

09:00 – 12:30 CDT

O’Kane, G

A phase 2 trial of first-line AZD0171 + durvalumab and chemotherapy (CT) in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) and CD8+ T cell infiltration

Abstract #CT126 / 9

Poster – TiP

Session PO.CT02.03 - Phase II Trials in Progress

11 April 2022

09:00 – 12:30 CDT

Purroy, N

First-in-human trial of intravenous MEDI9253, an oncolytic virus, in combination with durvalumab in patients with advanced solid tumors

Abstract #CT218 / 18

Poster – TiP

Session PO.CT01.03 - Phase I Trials in Progress 1

12 April 2022

09:00 – 12:30 CDT

Candido, J

AZD0171 (anti-LIF) combines productively with chemotherapy and anti-PD-L1 in mouse models of cancer

Abstract #1293 / 3

Poster

Session PO.IM02.08 - Immune Mechanisms Invoked by Other Therapies

11 April 2022

09:00 – 12:30 CDT

DDR

Yap, TA

PETRA: First in class, first in human trial of the next generation PARP1-selective inhibitor AZD5305 in patients (pts) with BRCA1/2, PALB2 or RAD51C/D mutations

Abstract #CT007

Oral

Session CTPL02 - Clinical Trials Targeting the DNA Damage Response and KRAS

10 April 2022

16:01 – 16:16 CDT

Pike, A

Evaluation of the CNS penetration of a next generation PARP inhibitor, AZD9574, in cynomolgus monkey using positron emission tomography

Abstract #5076

Poster

Session OPO.CH01.01 - Drug Discovery, Design, and Delivery

8 April 2022

12:00 – 13:00 CDT

Davies, BR

AZD9574 is a novel, brain penetrant PARP-1 selective inhibitor with activity in an orthotopic, intracranial xenograft model with aberrant DNA repair

Abstract #2609 / 22

Poster

Session PO.ET04.02 - DNA Damage Response and Repair

12 April 2022

09:00 – 12:30 CDT

Ghosh, A

Structure-based and property-based drug design of AZD9574, a CNS penetrant PARP1 selective inhibitor and trapper

Abstract #6302

Poster

Session OPO.CH01.01 - Drug Discovery, Design, and Delivery

8 April 2022

12:00 – 13:00 CDT

Schou, M

Discovery and preclinical validation of [11C]AZ3391: A first in class blood-brain barrier permeable, subtype selective PARP-1 PET radioligand

Abstract #5977

Poster

Session OPO.TB07.01 - In Vivo Imaging

8 April 2022

12:00 – 13:00 CDT

Shapiro, GI

 

Ceralasertib and olaparib in the treatment of homologous recombination repair (HRR)-deficient platinum-sensitive ovarian cancer after progression on PARP inhibitors

Abstract #CT201 / 1

Poster – TiP

Session PO.CT01.03 - Phase I Trials in Progress 1

12 April 2022

09:00 – 12:30 CDT

ADCs

Kinneer, K

 

Discovery and first disclosure of AZD8205, a B7-H4-targeted antibody-drug conjugate utilizing a novel topoisomerase I linker-warhead

Abstract #1765 / 17

Poster

Session PO.ET01.04 - Antibody-Drug Conjugates

11 April 2022

13:30 – 17:00 CDT

Wortmann, P

 

Development and implementation of image analysis-based Quantitative Continuous Score (QCS) for B7-H4 IHC to understand AZD8205 pharmacodynamics

Abstract #452 / 3

Poster

Session PO.BCS02.02 - Artificial Intelligence and Digital Pathology

10 April 2022

13:30 – 17:00 CDT

 

 

 

Wallez, Y

Activity and tolerability of combinations of trastuzumab deruxtecan (T-DXd) with inhibitors of the DNA damage response in preclinical models

Abstract #5298

Poster

Session OPO.ET07.01 - Biological Therapeutic Agents

8 April 2022

12:00 – 13:00 CDT

Mettetal, J

Activity and tolerability of combination of trastuzumab deruxtecan with the next generation PARP1-selective inhibitor AZD5305 in preclinical models

Abstract #1142 / 6

Poster

Session PO.ET05.02 - Preclinical and Clinical Pharmacology

11 April 2022

09:00 – 12:30 CDT

1AstraZeneca obtained full oncology rights to monalizumab from Innate Pharma in October 2018 through a co-development and commercialisation agreement initiated in 2015


Notes

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, 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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