OSI-774-302

Astellas Pharma Global Development, Inc. on behalf of OSI Pharmaceuticals, LLC

1 Astellas Way, Northbrook, Illinois, United States,

Clinical Trial Disclosure, Astellas Pharma Global Development, Inc. on behalf of OSI Pharmaceuticals, LLC, Astellas.resultsdisclosure@astellas.com

Clinical Trial Disclosure, Astellas Pharma Global Development, Inc. on behalf of OSI Pharmaceuticals, LLC, Astellas.resultsdisclosure@astellas.com

No

No

No

Final

11 Jun 2014

No

Yes

25 Jun 2014

Yes

The primary objective of this study is to assess the efficacy of single-agent, oral, once daily, erlotinib (150 mg/day) at increasing disease-free survival following complete surgical resection with or without adjuvant chemotherapy in patients who have Epidermal Growth Factor Receptor (EGFR) positive tumors.

This clinical study was written, conducted and reported in accordance with the protocol, ICH GCP Guidelines, and applicable local regulations, including the European Directive 2001/20/EC, on the protection of human rights, and with the ethical principles that have their origin in the Declaration of Helsinki. Astellas ensures that the use and disclosure of protected health information (PHI) obtained during a research study complies with the federal and/or regional legislation related to the privacy and protection of personal information.

26 Nov 2007

Yes

Yes

Spain: 62

United Kingdom: 41

Austria: 39

Belgium: 12

Czech Republic: 20

France: 49

Germany: 93

Greece: 8

Hungary: 59

Italy: 36

Argentina: 12

Australia: 24

Canada: 58

Poland: 94

Romania: 23

Russian Federation: 95

Korea, Republic of: 131

Taiwan: 42

United States: 352

1250

536

0

0

0

0

0

0

726

521

3

Overall Study (overall period)

Randomised - controlled

Yes

Erlotinib

Tarceva®

Tablet

Oral use

150 mg/day erlotinib orally

Placebo

Tablet

Oral use

placebo tablets once a day

Erlotinib

Tarceva®

Tablet

Oral use

150 mg/day erlotinib orally

Placebo

Tablet

Oral use

placebo tablets once a day

Placebo

Tablet

Oral use

placebo tablets once a day

Erlotinib

Tarceva®

Tablet

Oral use

150 mg/day erlotinib orally

RC: Erlotinib

RC: Placebo

BPC-NOLC: Erlotinib/Placebo

BPC-NOLC: Placebo Only

BPC-OLC: Erlotinib

RC: Erlotinib

RC: Placebo

BPC-NOLC: Erlotinib/Placebo

BPC-NOLC: Placebo Only

BPC-OLC: Erlotinib

DFS is the time from the date of randomization until the first day non-small cell lung cancer (NSCLC) relapse is documented by radiological exam and/or biopsy, or until death in the absence of relapse. After randomization, NSCLC relapse was based on radiological evidence or biopsy, as determined by the investigator. Participants without a DFS event were censored on the last adequate radiological assessment date. 99999 represents data not estimable.

Primary

Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter until the data cut-off date of 08 April 2013 (maximum time on follow-up was 64 months).

The null hypothesis that DFS distributions of the 2 arms were equivalent was tested using an unstratified 2-sided log-rank test at the 0.05 level. The primary analysis of DFS was performed when at least 410 events had accrued. If the result of the primary analysis of DFS was statistically significant favoring the erlotinib treatment arm, the null hypothesis of no treatment difference of key secondary efficacy variables was tested under a hierarchical testing procedure.

RC: Erlotinib v RC: Placebo

973

Pre-specified

0.9

2-sided

DFS is the time from the date of randomization until the first day that non-small cell lung cancer (NSCLC) relapse is documented by radiological exam and/or biopsy, or until death in the absence of relapse. After randomization, NSCLC relapse was based on radiological evidence or biopsy, as determined by the investigator. Participants without a DFS event were censored on the last adequate radiological assessment date.

Primary

Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter until the data cutoff date of 11 June 2014 (maximum time on follow-up was 78 months).

The null hypothesis that DFS distributions of the 2 arms were equivalent was tested using an unstratified 2-sided log-rank test at the 0.05 level.

RC: Erlotinib v RC: Placebo

973

Pre-specified

0.94

2-sided

Overall survival was defined as the time from the date of randomization until the documented date of death. Participants who were still alive were censored on the last day they were known to be alive. The overall survival data were not mature; 99999 represents data not estimable.

Secondary

Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter until the data cut-off date of 08 April 2013 (maximum time on follow-up was 64 months).

Overall survival was defined as the time from the date of randomization until the documented date of death. Participants who were still alive were censored on the last day they were known to be alive. The overall survival data were not mature; 99999 represents data not estimable.

Secondary

Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter until the data cut-off date of 11 June 2014 (maximum time on follow-up was 78 months).

Disease-free survival (DFS) is the time from the date of randomization until the first day NSCLC relapse is documented by radiological exam and/or biopsy, or until death in the absence of relapse. After randomization, NSCLC relapse was based on radiological evidence or biopsy, as determined by the investigator. Participants without a DFS event were censored on the last adequate radiological assessment date. Activating EGFR mutation-positive is defined as exon 19 deletion or exon 21 L858R (or both) detected.

Secondary

Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter until the data cut-off date of 08 April 2013 (maximum time on follow-up was 64 months).

Disease-free survival (DFS) is the time from the date of randomization until the first day NSCLC relapse is documented by radiological exam and/or biopsy, or until death in the absence of relapse. After randomization, NSCLC relapse was based on radiological evidence or biopsy, as determined by the investigator. Participants without a DFS event were censored on the last adequate radiological assessment date. Activating EGFR mutation-positive is defined as exon 19 deletion or exon 21 L858R (or both) detected. 99999 represents data not estimable.

Secondary

Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter until the data cut-off date of 11 June 2014 (maximum time on follow-up was 78 months).

Overall survival is defined as the time from the date of randomization until the documented date of death. Participants who were still alive were censored on the last day they were known to be alive. Activating EGFR mutation-positive is defined as exon 19 deletion or exon 21 L858R (or both) detected. The overall survival data were not mature; 99999 represents data not estimable.

Secondary

Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter until the data cut-off date of 08 April 2013 (maximum time on follow-up was 64 months)

Overall survival is defined as the time from the date of randomization until the documented date of death. Participants who were still alive were censored on the last day they were known to be alive. Activating EGFR mutation-positive is defined as exon 19 deletion or exon 21 L858R (or both) detected. The overall survival data were not mature; 99999 represents data not estimable.

Secondary

Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter until the data cut-off date of 11 June 2014 (maximum time on follow-up was 78 months).

An AE was defined as any untoward medical occurrence in a study participant and did not necessarily have a causal relationship with study treatment. An AE was considered serious if it resulted in death, a life-threatening situation, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect in the offspring of a participant, other important medical events, or is on the Astellas Always Serious List. A drug-related AE was any AE with at least a possible relationship to study treatment as assessed by the investigator. Severity was graded by the investigator according to the National Cancer Institute Common Terminology Criteria for Adverse Events, v3.0, where Grade 1=Mild AE; Grade=2 Moderate AE; Grade 3=Severe AE; Grade 4=Life-threatening or disabling; Grade 5=Death related to AE. AEs leading to death include deaths that occurred more than 30 days after the last dose of study drug.

Secondary

From the date of first dose of study drug until 30 days after the last dose. The median time on treatment was 11.9 months for erlotinib and 21.9 months for placebo. Data are based off the 11 June 2014 data cut-off date.

From the first dose of study drug until 30 days after the last dose. Maximum time on treatment for the Randomized Cohort was 24 months; maximum time on treatment for the BPC was 13 months on blinded study drug and 26 months on open-label erlotinib.

One participant in the Randomized Cohort assigned to the erlotinib arm received placebo instead due to a dispensing error and is included in the placebo group for safety analyses. For the Breached Protocol Cohort safety analyses are based on the total no open-label and open-label populations. Safety data are based on the 11 June 2014 cut-off date.

9.1

RC: Erlotinib

RC: Placebo

BPC-NOLC: Erlotinib/Placebo

BPC-NOLC: Placebo Only

BPC-OLC: Erlotinib