AstraZeneca, along with MedImmune, the company’s global biologics research and development arm, will illustrate the strength and depth of research underpinning its scientific leadership in oncology, at the European Cancer Congress (ECC) 2015 in Vienna, Austria (25-29 September 2015).
19 oral and poster presentations, including data on AZD9291, durvalumab and olaparib, will provide confirmation and complementary analysis of previously presented results, as well as new data on:
AZD9291: pooled Phase II efficacy and safety data in pre-treated patients with non-small cell lung cancer (NSCLC) (Abstract # 3113) and analysis of patients with and without brain metastases (Abstract # 3083)
Durvalumab (MEDI4736) monotherapy: preliminary results investigating tumour indicators of response in patients with NSCLC (Late Breaker Presentation Abstract # 15LBA)
Olaparib: tumour biomarkers to suggest potential treatment activity in women with ovarian cancer without a BRCA1/2 mutation (Abstract # 435)
Mondher Mahjoubi, Senior Vice President, Global Product Strategy for Oncology at AstraZeneca, said: “Data published at ECC 2015 confirm the strength and rapid progress of our development plan in oncology. Our large and growing dataset for AZD9291 is a great example of this, as it highlights the robustness and consistency of the results we are seeing across a broad population of pre-treated non- small cell lung cancer patients.”
AZD9291 in pre-treated patients with NSCLC
Data from an analysis of the AURA Phase II studies (AURA extension and AURA2) in pre-treated patients with NSCLC (Abstract # 3113) confirm findings already reported at previous congresses for AZD9291, a highly selective, irreversible inhibitor of both the activating epidermal growth factor receptor mutation (EGFRm) and the resistance mutation, T790M. Pooled data from over 400 pre-treated patients with EGFRm T790M showed an objective response rate (ORR) of 66% (95% confidence interval (CI) 61% to 71%).
ORR was consistent across all sub-groups treated with AZD9291 including ethnicity, tumour mutation types and presence/absence of brain metastases. Preliminary median progression free survival (PFS) was 9.7 months (95% CI 8.3 months to non-calculable [NC]) and median duration of response (DoR) was non-calculable (95% CI 8.3 months to NC).
The safety profile was also in line with previous data readouts. The most common all-causality adverse events (AEs) were diarrhoea, 42% (1% ≥Grade 3) and rashes (grouped terms), 41% (1% ≥Grade 3).
Reported AEs of hyperglycaemia, interstitial lung disease (ILD) and QT prolongation remained consistent with data previously presented: ILD and pneumonitis 3% (2% ≥Grade 3), hyperglycaemia 1% (0% ≥Grade 3), QT prolongation 4% (1% ≥Grade 3). There was a low discontinuation rate: 4% of patients discontinued AZD9291 due to drug-related AEs (as assessed by the investigator).
An analysis of AURA Phase II studies (Abstract # 3083) will demonstrate the consistent activity of AZD9291 in patients with EGFRm T790M NSCLC with and without brain metastases; clinical anecdotes suggest that AZD9291 may have activity in the brain. Pre-clinical data showing that AZD9291 penetrates the blood-brain-barrier were recently presented at the World Congress on Lung Cancer (WCLC Abstract # ID410). The BLOOM (NCT02228369) study is investigating further the potential activity of AZD9291 in the brain.
The AZD9291 ASTRIS study (NCT02474355) is recruiting pre-treated patients with advanced or metastatic EGFRm T790M NSCLC in a real-world setting at multiple sites in Europe. In the US, an expanded access programme (NCT02451852) for AZD9291 for patients with advanced or metastatic EGFRm T790M NSCLC is available. AZD9291 is an investigational therapy and is not yet approved for any indication in any market.
Immuno-oncology programme progresses at pace
MedImmune will demonstrate advances in biomarker research that may identify patients most likely to respond to immunotherapies. The research will demonstrate the potential association between increased tumour expression of programmed death ligand-1 (PD-L1) and gamma interferon and response to the PD-L1 mAb, durvalumab (MEDI4736) (Abstract # 15LBA).
The new research is part of the extensive durvalumab clinical development programme in NSCLC, which includes the PACIFIC (NCT02125461), ATLANTIC (NCT02087423), ARCTIC (NCT02352948), MYSTIC (NCT02453282) and NEPTUNE (NCT02542293) trials discussed recently at WCLC and other conferences this year.
Robert Iannone, Head of Immuno-Oncology, Global Medicines Development at AstraZeneca, said: “Advances in our biomarker development will enable us to effectively identify patients who could benefit most from durvalumab monotherapy as well as those for whom the combination with other immunotherapies such as our anti- CTLA-4 inhibitor (tremelimumab) would be more effective. These insights will support progress with our extensive late-stage immuno-oncology programme, which now includes 17 clinical studies and more than 9,000 patients in lung, bladder, head and neck, and other cancers.”
Olaparib shows activity beyond BRCA mutations
Exploratory biomarker data from a Phase II study of olaparib are contributing to an enhanced scientific understanding of why some women with ovarian cancer without a BRCA1/2 mutation demonstrate anti-tumour activity with poly ADP-ribose polymerase (PARP) inhibitor treatment (Abstract # 435). The data suggest that these women have tumours with mutations in other homologous recombination repair (HRR) genes that behave in a similar way to BRCA mutations.
The new biomarker analysis was carried out on tumour samples from 209 patients who took part in a Phase II trial of olaparib in platinum-sensitive relapsed serous ovarian cancer (NCT00753545, Study 19).
In a sub-set of patients whose tumours did not carry the BRCA mutation, there was a trend towards greater olaparib efficacy in 21 women with other HRR gene mutations compared to 58 patients with no detectable mutations in other HRR genes.
Olaparib is the cornerstone of AstraZeneca’s industry-leading pipeline of personalised treatments targeting DNA damage and repair mechanisms in cancer cells. The potential of olaparib to target tumours with HRR mutations beyond those in BRCA genes is under investigation in ongoing clinical trials.
AstraZeneca delivering on oncology strategy
ECC marks another successful milestone for AstraZeneca and MedImmune in 2015, following the launch of LYNPARZA™ (olaparib) in the U.S. and Europe, the approval of IRESSA® (gefitinib) in the US, rapid US and EU filings for AZD9291, key regulatory designations for further investigational compounds, and encouraging data supporting the company’s focus on combinations across immuno-oncology and small molecules.
As progress continues, the company is deepening its understanding of cancer biology and extending its research into a wider range of tumour types, with new data expected at congresses throughout 2016.
AstraZeneca remains on track to achieve its bold ambition of delivering six new cancer medicines to patients by 2020.