AstraZeneca advances its pipeline and highlights progress in immuno-oncology, ADCs, cell therapy and epigenetics at AACR
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 Biomedicine 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.