AstraZeneca advances its ambition to redefine cancer care with new data across its industry-leading and diverse pipeline in haematology at the 66^th American Society of Hematology (ASH) Annual Meeting and Exposition 7 to 10 December 2024.

A total of 57 abstracts will feature 13 approved and potential new medicines from across AstraZeneca’s portfolio and pipeline in haematology, including from Alexion, its rare disease group, with data in key settings including chronic lymphocytic leukaemia (CLL), multiple myeloma (MM), paroxysmal nocturnal haemoglobinuria (PNH) and other haematologic diseases.

Anas Younes, Senior Vice President, Haematology R&D, AstraZeneca, said: “Our data at ASH from the AMPLIFY Phase III trial will demonstrate the efficacy and safety of our leading second-generation BTK inhibitor, Calquence, as a fixed-duration therapy in first-line CLL. In addition, new results for our novel T-cell engager, AZD0486, will reinforce its promising clinical profile in lymphomas, and data for our novel CAR T cell therapy, AZD0120, will highlight the potential of this therapy to transform treatment in multiple myeloma.”

Christophe Hotermans, Senior Vice President, Head of Global Medical Affairs, Alexion, said: “Our ASH presentations will highlight the transformative impact of our medicines, including new analyses from the ALPHA Phase III trial reaffirming the safety and efficacy of our first-in-class Factor D inhibitor Voydeya as add-on to Ultomiris or Soliris for the subset of patients with PNH experiencing clinically significant extravascular haemolysis. Further, new insights from our robust pipeline will enhance the understanding of several rare haematologic and cardiovascular conditions, underscoring our commitment to innovation in rare disease.”

Calquence combinations demonstrate significant benefits across CLL and MCL

An oral presentation on interim results from the pivotal AMPLIFY Phase III trial will demonstrate the potential of fixed-duration Calquence in combination with venetoclax, with or without obinutuzumab, in previously untreated adults with CLL compared to standard-of-care chemoimmunotherapy.¹ These results will be featured during the ASH Press Briefing on Sunday 8 December.

An updated analysis from the pivotal ECHO Phase III trial will further highlight the use of Calquence in combination with bendamustine and rituximab as a first-line treatment option by demonstrating high and durable undetectable minimal residual disease (MRD) rates in previously untreated patients with mantle cell lymphoma (MCL) as well as showing the benefit of Calquence across all patients including those with high-risk disease characteristics.² Results from ECHO were first presented as a late-breaking oral presentation at the European Hematology Association (EHA) 2024 Hybrid Congress in June.³

Results will also be shared from the ChangE Phase III trial, evaluating Calquence compared with chlorambucil plus rituximab in first-line CLL in patients in China.⁴

New data show promise of next generation T-cell engagers and chimeric antigen receptor T-cell (CAR T) therapy

Two oral presentations will share results for the novel CD19xCD3 bispecific T-cell engager AZD0486, reinforcing the potential of this novel medicine as a new treatment option for B-cell malignancies.^5,6 Phase I results demonstrate high response rates, with a 96% overall response rate, 85% complete response rate and high rates of undetectable MRD in patients with relapsed/refractory follicular lymphoma (R/R FL) at doses of 2.4 mg and above.⁵ Additionally, interim Phase I results will show the early potential of AZD0486 in patients with heavily pretreated diffuse large B-cell lymphoma (DLBCL).⁶ Data will also reinforce the safety profile of AZD0486, with cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) events effectively mitigated by the double step-up dosing schedule.⁷   

Early data for AZD0120 (GC012F), a novel BCMAxCD19 dual-targeting autologous CAR T developed using the Gracell FasTCAR  rapid manufacturing process, will show potential as a first-line therapy for elderly patients with newly diagnosed transplant ineligible MM.⁸ Preliminary results from the ongoing investigator-initiated trial of AZD0120 suggest deep responses and an acceptable safety profile, with no ICANS and no ≥Grade 2 CRS events observed in this patient population.⁸

An oral presentation will share preclinical data demonstrating the anti-tumour activity of AZD5492, a next-generation CD8 selective, CD20-targeting T-cell engager, designed using AstraZeneca’s innovative Target Induced T-cell Activating Nanobody (TITAN) platform. AZD5492 is currently being evaluated in Phase I clinical trials in R/R Non-Hodgkin lymphoma (NHL) and CLL.⁹

Voydeya (danicopan) as add-on to Ultomiris (ravulizumab) or Soliris (eculizumab) demonstrates low rate of mild or moderate BTH events and improves quality of life measures in patients with PNH and clinically significant EVH

Data will be presented detailing events of breakthrough haemolysis (BTH), a key indicator of intravascular haemolysis and PNH disease control, reported in the ALPHA trial evaluating Voydeya as add-on to Ultomiris or Soliris in patients with PNH experiencing clinically significant extravascular haemolysis (EVH) and separately in the PEGASUS Phase III trial evaluating pegcetacoplan in patients with PNH previously treated with Soliris. Data will show that 5/84 patients (6.0%) in the ALPHA trial and 19/80 patients (23.8%) in the PEGASUS trial experienced one or more BTH events. Moreover, most BTH events (6/7 or 85.7%) in the ALPHA trial were either mild or moderate, and all events were resolved without transfusion, dose modification or treatment withdrawal.¹⁰

Separately, final long-term patient-reported outcomes from the ALPHA trial will demonstrate Voydeya as add-on to Ultomiris or Soliris resulted in sustained improvements in fatigue, quality of life and physical function for up to 72 weeks in the subset of patients with PNH who experience clinically significant EVH.¹¹