IRIS Study: Reevaluating First-Line

CML Therapy

􀂄 Gleevec® versus IFN-α + ara-C (Study 106)

􀂄 Rationale for first-line use of Gleevec

– High response rate in patients failing IFN-α

– Higher response rates in earlier phases

􀂄 Phase III, multinational, randomized, open-label

􀂄 Inclusion criteria: newly diagnosed chronic phase CML patients

􀂄 Primary objective—determine time to progression, defined as:

– Increasing WBC count

– Loss of CHR or MCR

– Accelerated phase or blast crisis

– Death

􀂄 Secondary objectives—determine rate and duration of

CHR and MCR; overall survival; safety; molecular response;

quality of life (QoL) using FACT-BRM

[slide 12]

IRIS Study: Reevaluating First-Line CML Therapy1,2

• The International Randomized Interferon Versus STI571 (IRIS) study is a phase III trial comparing Gleevec® with IFN-α combined with cytarabine (ara-C) in patients with newly diagnosed, previously untreated, Ph+ CML in chronic phase.

• The rationale for first-line use of Gleevec was the high response rate in patients for whom IFN-α had

failed and the evidence that earlier use of Gleevec induces higher response rates.

• Patients with Ph+ chronic phase CML had to be enrolled within 6 months of diagnosis.

• Patients had to have no prior therapy except hydroxyurea or anagrelide.

• The primary endpoint is progression-free survival (time to progression) in the 2 randomized patient populations, where progression is defined as any of the following:

– Increasing WBC counts in patients without a complete hematologic response

– Loss of a complete hematologic response or major cytogenetic response

– Progression to accelerated phase or blast crisis

– Death

• Secondary objectives include determining:

– The rate and duration of CHR and MCR

– Safety and tolerability

– Overall survival

– Molecular response (assessed by RT-PCR for bcr-abl expression) in patients achieving

a complete cytogenetic response

– Quality of life (QoL) using the Functional Assessment of Cancer Therapy - Biologic Response

Modifier (FACT-BRM). FACT-BRM is an instrument typically used to assess general effects of

interferon toxicity

References

1. Gleevec® (imatinib mesylate) Prescribing Information. East Hanover, NJ: Novartis Pharmaceuticals Corporation;

2003.

2. Data on file. Novartis Pharmaceuticals Corporation, East Hanover, NJ.