AstraZeneca advances its pipeline and highlights progress in immuno-oncology, ADCs, cell therapy and epigenetics at AACR
Novel Imfinzi-based regimen significantly improved patient outcomes in resectable non-small cell lung cancer in AEGEAN Phase III trial.
Strength of emerging proprietary antibody drug conjugates technology demonstrated with data across three assets.
First clinical data for CAR-T cell therapy in solid tumours utilising AstraZeneca’s innovative research and armouring platform.
AstraZeneca will present new data across its diverse, industry-leading Oncology pipeline and portfolio at the American Association for Cancer Research (AACR) Annual Meeting, 14 to 19 April 2023.
Data from 70 presentations will be featured, including eight oral presentations, a plenary presentation of the AEGEAN Phase III trial of Imfinzi (durvalumab) based regimen in resectable non-small cell lung cancer (NSCLC), and the first disclosures of preclinical data for five novel molecules across the Company’s Antibody Drug Conjugate (ADC), Cell Therapy and Epigenetics scientific platforms.
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “It’s exciting to see our strategy to attack cancer from multiple angles come to life at AACR this year through data from our proprietary antibody drug conjugates, next generation cell therapies and epigenetics molecules. Furthermore, results from the AEGEAN trial show the potential of treating lung cancer patients early with Imfinzi before and after surgery which reinforces the importance of diagnosing lung cancer early.”
Improving outcomes for patients with resectable lung cancer with Imfinzi
A late-breaking presentation of the AEGEAN Phase III trial results will highlight the potential of a novel Imfinzi-based treatment before and after surgery for patients with resectable early-stage (IIA-IIIB) NSCLC. AEGEAN has met its two primary endpoints, demonstrating improvements in event-free survival and pathologic complete response with Imfinzi in combination with neoadjuvant chemotherapy before surgery and as adjuvant monotherapy versus neoadjuvant chemotherapy alone followed by surgery.
Delivering the next wave of ADCs with proprietary platform
Two oral presentations will feature the first preclinical and translational results for AZD9592, a bispecific ADC designed to deliver targeted chemotherapy to cancer cells with a topoisomerase inhibitor 1 (TOP1i) warhead using the Company’s proprietary linker technology.
AZD9592 binds to two known oncogenic drivers: epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (cMET). These two drivers are often co-expressed in solid tumours including in NSCLC and head and neck squamous cell carcinoma (HNSCC). This is the Company’s first bispecific ADC to enter the clinic and shows a promising efficacy and safety profile in preclinical models, with evidence for DNA damage dependent tumour cell death as the mechanism of action.
In addition, the first preclinical results will be presented for another ADC, AZD5335, a promising therapeutic candidate for the treatment of certain ovarian cancers. This ADC has a folate receptor alpha (FRα) targeting antibody linked to a proprietary TOP1i warhead. A robust anti-tumour response is reported in FRα-expressing preclinical models that are resistant to another FRα ADC with a microtubule inhibitor warhead. In addition, AZD5335 is active in models with either high or low levels of target expression as detected by computational pathology.
Preclinical data for AZD8205, an ADC targeting B7-H4, will also be presented both as monotherapy and in combination with the PARP-1 selective inhibitor, AZD5305. Robust anti-tumour activity is evident in preclinical models across multiple B7-H4 positive tumour types, including ovarian and cholangiocarcinoma tumours, with combination therapy resulting in higher anti-tumour activity than monotherapy.
Building the next generation of cell therapies in solid tumours
In cell therapy, the first clinical data will be presented for C-CAR031, a novel transforming growth factor-beta (TGFβ) armoured Glypican 3 (GPC3) targeting chimeric antigen receptor T cell (CAR-T) therapy that is being investigated for liver cancer. Early results show it is well tolerated with promising anti-tumour activity seen with objective responses in several patients to date.
The CAR-T is based on AZD5851, a novel cell therapy that was designed by AstraZeneca, and is being developed and manufactured by Cellular Bioscience Medicine group (CBMG). AstraZeneca’s TGFβ armouring is designed to resist the immuno-suppressive tumour microenvironment and enhance the potential effectiveness of CAR-Ts in solid tumours.
In addition, the first preclinical data will be shared on AZD0754, a novel TGFβ armoured CAR-T targeting STEAP2, a protein commonly overexpressed in prostate cancer. This is the first cell therapy to be designed, manufactured and developed by AstraZeneca. The presentation will show encouraging preclinical safety data and supports future clinical development of this potential first-in-class CAR-T therapy.
First disclosure and preclinical data for an epigenetics molecule targeting PRMT5
Epigenetic therapy is one of AstraZeneca’s six core scientific areas of focus. The modality is the latest addition to the Company’s diverse portfolio, which is designed to attack cancer from multiple angles and redefine outcomes for patients with high unmet needs.
At AACR, the first preclinical data will be presented for the novel lead epigenetics molecule, AZ-PRMT5i-1, a potent methylthioadenosine phosphorylase (MTAP)-selective PRMT5 inhibitor with anti-tumour activity in MTAP-deleted tumours. Loss of the MTAP gene occurs across approximately 15% of all cancers, which provides an opportunity to use a biomarker selection strategy and also spare healthy tissue. The preclinical results demonstrate MTAP selectivity and promising anti-tumour activity.
Harnessing transformational technologies
Transformational technologies, including circulating tumour DNA (ctDNA), computational pathology, and data science and artificial intelligence (AI), underpin the success of progressing AstraZeneca’s pipeline. Several presentations at AACR showcase the Company’s efforts to harness the power of these technologies to better understand complex cancer biology, identify and select patients for treatment and increase the probability of success in the clinic.
Key AstraZeneca presentations during AACR 2023
Lead author | Abstract title | Presentation details |
IO | ||
Heymach, JV | CT005 - AEGEAN: A phase 3 trial of neoadjuvant durvalumab + chemotherapy followed by adjuvant durvalumab in patients with resectable NSCLC | Abstract #CT005Plenary Harnessing the Immune System in the Clinic 16 April 202314:45 – 15:00 ET |
Iyer S | Immunomodulatory effects of ceralasertib in combination with durvalumab in NSCLC patients with progression on anti-PD-(L)1 treatment (HUDSON, NCT03334617) | Abstract #CT039Clinical Trials MinisymposiumNovel Immunotherapy Combination Clinical Trials18 April 202315:50 – 16:00 ET |
ADCs | ||
Gymnopoulos, M | First disclosure of AZD5335, a TOP1i-ADC targeting low and high FRα-expressing ovarian cancer with superior preclinical activity vs FRα-MTI ADC | Abstract #LB025 / 17PosterLate-Breaking Research: Experimental and Molecular Therapeutics 116 April 202313:30 – 17:00 ET |
Comer, F | AZD9592: an EGFR-cMET bispecific antibody-drug conjugate (ADC) targeting key oncogenic drivers in non-small-cell lung cancer (NSCLC) and beyond | Abstract #5736MinisymposiumNew Tricks for Known Targets: Novel Approaches to Inhibit Oncogenic Signaling 18 April 202315:22 – 15:37 ET |
McGrath, L | Evaluation of the relationship between target expression and in vivo anti-tumour efficacy of AZD9592, an EGFR/c-MET targeted bispecific antibody drug conjugate | Abstract #5737MinisymposiumNew Tricks for Known Targets: Novel Approaches to Inhibit Oncogenic Signaling 18 April 202315:37 - 15:52 ET |
Cazes, A | Preclinical evaluation of a novel B7-H4-targeted antibody-drug conjugate AZD8205 as a single agent and in combination with novel PARP inhibitor and checkpoint blockade | Abstract #2947 / 25PosterTherapeutic Antibodies 217 April 202313:30 - 17:00 ET |
Meric-Bernstam, F | TROPION-PanTumor03: Phase 2, multicenter study of datopotamab deruxtecan (Dato-DXd) as monotherapy and in combination with anticancer agents in patients (pts) with advanced/metastatic solid tumours | Abstract #CT058 / 16PosterPhase II and Phase III Clinical Trials in Progress17 April 20239:00 - 12:30 ET |
Bhavsar, D | Combination of T-DXd with the irreversible pan-HER TKI afatinib drives combination benefit in HER2-low gastric and lung tumours | Abstract #3999 / 22PosterOncogenes and Tumour Suppressor Genes as Targets for Therapy 3 18 April 20239:00 - 12:30 ET |
Wray, R. | Improving Treatment Outcomes: A Digital Solution for Remote Patient Monitoring of Stomatitis for Patients receiving Dato-DXd | Abstract #LB143 / 7PosterLate-Breaking Research: Population Sciences17 April 202313:30 - 17:00 ET |
Cell Therapy | ||
van Dyk, D | Antitumour activity of AZD0754, a dnTGFbR2 armored STEAP2 targeted CAR-T therapy, in preclinical models of prostate cancer | Abstract #LB085 / 1PosterLate-Breaking Research: Immunology 117 April 20239:00 - 12:30 ET |
Zhang, Q | First report of preliminary safety, efficacy, and pharmacokinetics of C-CAR031 (GPC3-specific TGFBRIIDN CAR-T) in patients with advanced HCC | Abstract #CT097 / 5PosterFirst-in-Human Phase I Clinical Trials 117 April 202313:30 - 17:00 ET |
Epigenetics | ||
Smith, JM | Identification of a novel series of MTAP-selective PRMT5 inhibitors, and first disclosure of AZ-PRMT5i-1 | Abstract #3088 / 1PosterTargeted Drug Design and Development for Cancer Therapy 17 April 202313:30 - 17:00 ET |
Lynch, J | AZ-PRMT5i-1: A potent MTAP-selective PRMT5 inhibitor with pharmacodynamic and monotherapy anti-tumour activity in MTAP-deleted tumours | Abstract #6272 / 10PosterEpigenetics19 April 20239:00 - 12:30 ET |
TDR1 | ||
Zhi Peng | A Multicenter Phase II Study of Savolitinib in Patients with MET-Amplified Gastroesophageal Junction Adenocarcinomas or Gastric Cancer | Abstract # CT152Phase II Clinical Trials 117 April 2023 13:30 - 17:00 ET |
ctDNA | ||
Labrousse, P | The evolution of MRD assays; moving beyond the tumour-informed bespoke NGS panel | Abstract #LB293 / 6PosterLate-Breaking Research: Clinical Research 319 April 20239:00 - 12:30 ET |
Russell, H | Evaluation of a tumour informed MRD assay with contrived breast cancer samples | Abstract #3384 / 27PosterLiquid Biopsies: Circulating Nucleic Acids and Circulating Tumour Cells 317 April 202313:30 - 17:00 ET |
Munugalavadla V | Utility of ctDNA-based targeted methylation MRD assay for hematological malignancies | Abstract #3369 / 12PosterLiquid Biopsies: Circulating Nucleic Acids and Circulating Tumour Cells 317 April 202313:30 - 17:00 ET |
Hartmaier, R | Baseline and on-treatment plasma-based genomics as a predictor of outcomes in SAVANNAH: savolitinib + osimertinib in EGFRm MET overexpressed/amplified NSCLC post-osimertinib | Abstract #LB294 / 7PosterLate-Breaking Research: Clinical Research 319 April 20239:00 - 12:30 ET |
Data Science & AI | ||
Arango G | Translating state-of-the-art deep learning predictions of IO treatment efficacy to clinical practice | Abstract #5359 / 8PosterArtificial Intelligence and Machine/Deep Learning 118 April 202313:30 - 17:00 ET |
Arango G | Enhancing the utilization of deep learning to predict patient response in small immunotherapy cohorts using real world data | Abstract #1174MinisymposiumAdvancing Cancer Research Through an International Cancer Registry: AACR Project GENIE Use Cases16 April 202315:36 - 15:51 ET |
Nikolau N | Improving survival prediction using flexible late fusion machine learning framework for multi-omics data integration | Abstract #5395 / 11PosterArtificial Intelligence and Machine/Deep Learning 218 April 202313:30 - 17:00 ET |
Arango G | Improved identification of CHIP mutations from cell free DNA without matched normal samples using machine learning | Abstract #5360 / 9PosterArtificial Intelligence and Machine/Deep Learning 118 April 202313:30 - 17:00 ET |
Ellen JG | Autoencoder-based multimodal prediction of survival for non-small cell lung cancer | Abstract #5373 / 22PosterArtificial Intelligence and Machine/Deep Learning 118 April 202313:30 - 17:00 ET |
Computational Pathology | ||
Potdevin, G | A first assessment of CD8-PET/CT with 89-Zr-Crefmirlimab as predictive biomarker for response to standard of care immunotherapy in patients with solid tumours | Abstract #3577 / 2PosterPET, MRI, and CT Imaging18 April 20239:00 - 12:30 ET |
Brieu, N | A unified computational pathology method to quantify HER2 expression from raw IHC and IF images in breast cancer | Abstract #5388 / 4PosterArtificial Intelligence and Machine/Deep Learning 218 April 202313:30 - 17:00 ET |
1 Tumour Drivers and resistance
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.
Contacts
For details on how to contact the Investor Relations Team, please click here. For media contacts, click here.