8273-CL-0302

Astellas Pharma Global Development, Inc.

1 Astellas Way, Northbrook, Illinois, United States, 60062

Clinical Trial Disclosure, Astellas Pharma Global Development, Inc., 1800 888-7704, astellas.resultsdisclosure@astellas.com

Clinical Trial Disclosure, Astellas Pharma Global Development, Inc., 1800 888-7704, astellas.resultsdisclosure@astellas.com

No

No

No

Final

21 Dec 2017

No

Yes

21 Dec 2017

No

The primary objective of this study was to evaluate the progression free survival (PFS), based on independent radiologic review (IRR) of ASP8273 compared to erlotinib or gefitinib in patients with locally advanced, metastatic or unresectable stage IIIB/IV adenocarcinoma non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) activating mutations.

This clinical study was written, conducted and reported in accordance with the protocol, International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (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, national and/or regional legislation related to the privacy and protection of personal information.

11 Feb 2016

Yes

Yes

Australia: 23

Belgium: 4

Canada: 6

Chile: 8

France: 19

Germany: 17

Hungary: 4

Italy: 37

Japan: 128

Korea, Republic of: 65

Malaysia: 42

Netherlands: 4

Peru: 7

Portugal: 3

Romania: 8

Russian Federation: 5

Singapore: 8

Spain: 21

Taiwan: 37

Thailand: 27

Ukraine: 6

United Kingdom: 5

United States: 46

530

122

0

0

0

0

0

0

530

0

0

Overall Study (overall period)

Randomised - controlled

Yes

ASP8273

Capsule

Oral use

Participants received ASP8273 300 mg orally once daily on an empty stomach (no food for at least 2 hours before and 1 hour after taking drug) at approximately the same time every day.

Erlotinib

Tablet

Oral use

Participants received erlotinib 150 mg orally once daily on an empty stomach (no food for at least 2 hours before and 1 hour after taking drug) at approximately the same time every day. At the beginning of the trial, prior to site initiation and shipment of study drug supplies, each investigator selected either erlotinib or gefitinib to be utilized for all participants randomized to the comparator arm at their site.

Gefitinib

Tablet

Oral use

Participants received gefitinib 250 mg was taken orally once daily with water, with or without food, at approximately the same time every day. At the beginning of the trial, prior to site initiation and shipment of study drug supplies, each investigator selected either erlotinib or gefitinib to be utilized for all participants randomized to the comparator arm at their site.

ASP8273

Erlotinib or Gefitinib

ASP8273

Erlotinib or Gefitinib

PFS was defined as the time from the date of randomization until the date of radiological disease progression or until death due to any cause, based on the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as assessed by IRR. Results are based Kaplan-Meier estimate. The analysis population was the full analysis set (FAS), which consisted of all participants who were randomized. If a participant had neither progressed nor died, who received any further anticancer therapy for the disease before radiological progression, the participant was censored at the date of last radiological assessment. If progression or death occurred after missing 2 scheduled radiological assessments, the participant was censored at the date of last radiological assessment or at the date of randomization if no post-baseline radiological assessment was available. Data could not be calculated due to low number of events, and is denoted as "99999."

Primary

From date of randomization up to data cut-off date 09 May 2017 (approximately 15 months)

Comparison between ASP8273 and Erlotinib or Gefitinib treatment groups was performed using log-rank test stratified by ECOG (0 and 1 vs 2), EGFR mutation type (exon 19 deletion or exon 21 L858R) and TKI chosen by the site (erlotinib or gefitinib) before randomization. Comparison was tested at 1-sided significance level of 0.025. Hazard ratio based on Cox proportional hazards model. Assuming proportional hazards, HR < 1 indicated a reduction in hazard rate in favor of ASP8273 treatment group.

ASP8273 v Erlotinib or Gefitinib

530

Pre-specified

1.611

2-sided

All events of death after the first study drug administration were included. The analysis population was the safety analysis set (SAF), which consisted of all participants who took at least one dose of study drug.

Secondary

From date of randomization up to data cut-off date 21 Dec 2017 (approximately 22 months)

Percentage of participants with OR was defined as the proportion of participants with best overall response as complete response (CR) or partial response (PR) without confirmation based on the RECIST v1.1 as assessed by the blinded IRR. CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters. The analysis population was the FAS.

Secondary

From date of first dose of study drug up to data cut-off date 09 May 2017 (approximately 15 months)

Comparison between ASP8273 and Erlotinib or Gefitinib treatment groups was performed using stratified Cochran–Mantel–Haenszel (CMH) test, stratified by ECOG (0 and 1 vs 2), EGFR mutation type (exon 19 deletion or exon 21 L858R) and TKI chosen by the site (erlotinib or gefitinib) before randomization. Comparison was tested at 1-sided significance level of 0.025.

ASP8273 v Erlotinib or Gefitinib

530

Pre-specified

PFS was defined as the time from the date of randomization until the date of radiological disease progression or until death due to any cause, based on RECIST V1.1, as assessed by local investigator. Results are based Kaplan-Meier estimate. The analysis population was the FAS. If a participant had neither progressed nor died, who received any further anticancer therapy for the disease before radiological progression, the participant was censored at the date of last radiological assessment. If progression or death occurred after missing 2 scheduled radiological assessments, the participant was censored at the date of last radiological assessment or at the date of randomization if no post-baseline radiological assessment was available. Data could not be calculated due to low number of events, and is denoted as "99999."

Secondary

From date of randomization up to data cut-off date 09 May 2017 (approximately 15 months)

Comparison between ASP8273 and Erlotinib or Gefitinib treatment groups was performed using log-rank test stratified by ECOG (0 and 1 vs 2), EGFR mutation type (exon 19 deletion or exon 21 L858R) and TKI chosen by the site (erlotinib or gefitinib) before randomization. Comparison was tested at 1-sided significance level of 0.025. Hazard ratio based on Cox proportional hazards model. Assuming proportional hazards, HR < 1 indicated a reduction in hazard rate in favor of ASP8273 treatment group.

ASP8273 v Erlotinib or Gefitinib

530

Pre-specified

1.674

2-sided

Percentage of participants with disease control was defined as the proportion of participants whose best overall response was rated as CR, PR or stable disease (SD) among all analyzed participants based on RECIST V1.1. CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters. SD was defined as neither sufficient decrease to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference the smallest sum of diameters while on study drug. The analysis population was the FAS.

Secondary

From date of first dose of study drug up to data cut-off date 09 May 2017 (approximately 15 months)

Comparison between ASP8273 and Erlotinib or Gefitinib treatment groups was performed using stratified Cochran–Mantel–Haenszel (CMH) test, stratified by ECOG (0 and 1 vs 2), EGFR mutation type (exon 19 deletion or exon 21 L858R) and TKI chosen by the site (erlotinib or gefitinib) before randomization. Comparison was tested at 1-sided significance level of 0.025

ASP8273 v Erlotinib or Gefitinib

530

Pre-specified

DOR was defined as the time from the date of the first response CR/PR (whichever was first recorded) as assessed by IRR to the date of radiographical progression or date of censoring. If a participant had not progressed, the participant was censored at the date of last radiological assessment or at the date of first CR/PR if no post-baseline radiological assessment was available. Results are based Kaplan-Meier estimate. The analysis population was the FAS. Only participants with best overall response as CR or PR (without confirmation) were included in the analysis. Data could not be calculated due to low number of events, and is denoted as "99999."

Secondary

From date of first response up to data cut-off date 09 May 2017 (approximately 15 months)

Comparison between ASP8273 and Erlotinib or Gefitinib treatment groups was performed using log-rank test stratified by ECOG (0 and 1 vs 2), EGFR mutation type (exon 19 deletion or exon 21 L858R) and TKI chosen by the site (erlotinib or gefitinib) before randomization. Comparison was tested at 1-sided significance level of 0.025. Hazard ratio based on Cox proportional hazards model. Assuming proportional hazards, HR < 1 indicated a reduction in hazard rate in favor of ASP8273 treatment group.

ASP8273 v Erlotinib or Gefitinib

214

Pre-specified

1.298

2-sided

Safety was assessed by AEs, which included abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant. A treatment-emergent AE (TEAE) was defined as an AE observed after starting administration of the study drug. AEs were considered serious (SAEs) if the AE resulted in death, was life threatening, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, resulted in congenital anomaly, or birth defect or required inpatient hospitalization or led to prolongation of hospitalization. The analysis population was the safety analysis set (SAF), which consisted of participants who took at least 1 dose of study drug.

Secondary

From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 09 May 2017

FACT-EGFRI-18 is an 18-item Likert-scaled questionnaire, used to assess the effect of EGFR inhibitors on quality of life (QoL). The questionnaire is arranged in three HRQL dimensions: physical (seven items), social/emotional (six items), and functional well-being (five items). The response scores ranged from 0 to 4, and the response categories include “not at all”, “a little bit”, “somewhat”, “quite a bit”, and “very much.” Negatively worded items (e.g., “My skin bleeds easily “or “My skin condition affects my mood”) are reverse-scored, so that participants who experience a higher impact of symptom burden on HRQL receive a lower score (range 0-72). The analysis population was the SAF.

Secondary

Day 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months)

The EORTC-QLQ-LC13 is a validated module of the EORTC-QLQ-Core 30, which includes module items that evaluate symptoms such as cough, hemoptysis, shortness of breath, sore mouth or tongue, dysphagia, tingling hands or feet, hair loss and pain. The total score for the questionnaire ranges from 0 to 100. A high score for a functional scale represents a high/healthy level of functioning whereas a high score for a symptom scale or item represents a high level of symptomatology or problems. The analysis population was the SAF.

Secondary

Day 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months)

EORTC-QLQ-LC13 is a 30-item cancer-specific questionnaire with multitrait scaling was used to create five functional domain scales: Physical, Role, Emotional, Social and Cognitive; two items evaluate global QoL; in addition, three symptom scales assess Fatigue, Pain and Emesis; and six single items assess other symptoms. The total score ranges from 0 to 100, with a high score for a functional scale representing a high/healthy level of functioning and a high score for a symptom scale or item representing a high level of symptomatology or problems. The analysis population was the SAF.

Secondary

Day 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months)

The EQ-5D is a generic preference-based measure that indirectly measures the utility for health that generates an index-based summary score based upon societal preference weights. The EQ-5D-5L consists of 6 items that cover 5 main domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a general visual analog scale (VAS) for health status. Each item has 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity). The VAS ranges from 0 (worst health status) and 100 (best health status). The analysis population was the SAF.

Secondary

Day 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months)

From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 21 Dec 2017 (approximately 22 months)

18.0

Erlotinib or Gefitinib

ASP8273