AstraZeneca Announces First Phase II Results for ZD1839 in Advanced Non-Small Cell Lung Cancer.

Business Editors/Health & Medical Writers

WILMINGTON, Del.--(BW HealthWire)--Nov. 1, 2001

Data announced today at the 12th AACR-NCI-EORTC International Conference on 'Molecular Targets and Cancer Therapeutics', Miami, USA

Preliminary data from the first Phase II trial of ZD1839 (IRESSA(R)) presented today reported a combined total of objective responses or disease stabilization in more than 50% of patients who had advanced non-small cell lung cancer (NSCLC) which had progressed following other treatments.

ZD1839 is a once-daily, orally administered, selective EGFR-TKI (epidermal growth factor receptor-tyrosine kinase inhibitor).

ZD1839 is a small molecule that blocks tyrosine kinase (TK) activity on the epidermal growth factor receptor (EGFR) within the cell. EGFR-TK is an enzyme that regulates intracellular signaling pathways implicated in cancer cell proliferation and survival. Receptors for EGF and related growth factors play a major role in the biology of cancer cells in many solid tumors.

ZD1839 is being evaluated as a treatment in a broad range of common types of cancer.

Jose Baselga, M.D., one of the lead investigators in the study from Vall d'Hebron University Hospital, Barcelona, Spain, said today, "Lung cancer kills more people each year than prostate and breast cancer put together, yet treatment options for this devastating disease are still limited. Research on new treatment approaches like ZD1839 are badly needed. Non-small cell lung cancer is a challenging disease and studies of this approach represent a significant step forward."

In the international non-small cell lung cancer trial presented today, 210 patients were studied in a randomized, double-blind study which evaluated two dosages of oral ZD1839 (250mg/day and 500mg/day) taken as monotherapy.

Patients included in the study had previously progressed on one or two cytotoxic (chemotherapy) regimens, at least one of which contained platinum, and had no further standard treatment options available to them. The primary objectives of this study were to evaluate the objective tumor response rate and characterize the safety profile of the two ZD1839 doses tested.

Important secondary objectives included assessment of disease-related symptom relief and disease control rate.

During the study, tumors were assessed every four weeks for the first four months and then every eight weeks thereafter until disease progression. Study results presented today include preliminary results in 208 patients after a minimum of four months follow-up. The overall tumor response rate was 18.7% (39 patients out of 208).

A secondary end point, overall disease control rate, was 52.9% (tumor responses + disease stabilization was seen in 110 out of 208 patients). 34% (71 out of 208) of patients in the study remained progression free after four months. All of the efficacy results were similar between the 250 and 500mg/day doses.

An important secondary end point included prospectively in this trial was estimated time to disease related symptom relief including patient reported ease of breathing and less coughing and chest tightness. The overall disease related symptomatic improvement rate was 38.7% with a median time to improvement of eight days.

In this study, the most frequently occurring drug-related adverse events were mild skin reactions and diarrhea. The drug related adverse events with ZD1839 were dose dependent with fewer events and less severity at the 250mg/day dose.

For the 250mg/day dose the incidence for rash and diarrhea was 47% and 40%, respectively; for the 500mg/day dose the incidence for rash and diarrhea was 69% and 58%, respectively. In most cases these events did not require specific therapeutic intervention. Serious adverse events were uncommon and usually related to disease progression.

9.4% of patients on 500mg/day withdrew due to drug related adverse events compared with only 1.9% of those on 250mg/day.

A second similar Phase II study (IDEAL II) is near completion in the United States evaluating ZD1839 as a monotherapy in NSCLC patients who had received at least two prior chemotherapy regimens and who experienced disease progression or unacceptable toxicity from their most recent therapy.

In addition, two large studies evaluating ZD1839 given as a first-line treatment for NSCLC in combination with commonly used types of chemotherapy are fully recruited with results expected next year.

Additional data presented this week at the AACR-NCI-EORTC meeting highlighted the ongoing evaluation of ZD1839 in a range of tumor types:

-- A Phase I study assessing the tolerability, efficacy and

pharmacokinetics of ZD1839 in combination with gemcitabine and

cisplatin in patients with a variety of primary tumors.

-- A Phase I study evaluating ZD1839 in combination with

fluorouracil and leucovorin in patients with advanced

colorectal cancer.

-- Pre-clinical data on the effects of ZD1839 in combination with

tamoxifen (Nolvadex(R)) in breast cancer cell lines.

About AstraZeneca:

AstraZeneca continues its tradition of research excellence and innovation in Oncology harnessing rational drug design technologies to develop new compounds that offer advantages over current cytotoxic and hormonal treatment options.

The company has over 20 different anti-cancer projects in research and development including a range of novel targeted products such as anti-proliferatives, anti-angiogenesis, vascular targeting and anti-invasive agents.

AstraZeneca (NYSE:AZN) is a major international healthcare business engaged in the research, development, manufacture and marketing of ethical (prescription) pharmaceuticals and the supply of healthcare services.

It is one of the top five pharmaceutical companies in the world with healthcare sales of $15.8 billion and leading positions in sales of gastrointestinal, oncology, anesthesia (including pain management), cardiovascular, central nervous system (CNS) and respiratory products. In the United States, AstraZeneca is an $8 billion healthcare business with more than 10,000 employees.