7465-CL-0301

Astellas Pharma Global Development, Inc.

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

Clinical Trial Disclosure, Astellas Pharma Global Development, Inc., astellas.resultsdisclosure@astellas.com

Clinical Trial Disclosure, Astellas Pharma Global Development, Inc., astellas.resultsdisclosure@astellas.com

No

No

No

Interim

15 Jul 2020

Yes

15 Jul 2020

No

The purpose of this study was to compare the overall survival (OS) of participants with locally advanced or metastatic urothelial cancer treated with enfortumab vedotin (EV) to the OS of participants treated with chemotherapy.

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.

27 Jun 2018

Yes

Yes

Argentina: 2

Australia: 13

Austria: 8

Belgium: 28

Canada: 52

Denmark: 13

France: 54

Germany: 13

Italy: 19

Japan: 86

Korea, Republic of: 90

Netherlands: 13

Portugal: 4

Russian Federation: 5

Spain: 55

Switzerland: 3

Taiwan: 18

United Kingdom: 45

United States: 87

608

207

0

0

0

0

0

0

219

384

5

Overall Study (overall period)

Randomised - controlled

Yes

Enfortumab Vedotin

Powder for infusion

Intravenous use

Participants received 1.25 mg/kg of body weight enfortumab vedotin by intravenous (IV) infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle.

Docetaxel

Solution for infusion

Intravenous use

Participants received either 75 mg/m^2 docetaxel by IV infusion over approximately 1 hour on day 1 of every 21-day cycle.

Vinflunine

Concentrate for solution for infusion

Intravenous use

Participants received 320 mg/m^2 vinflunine by IV infusion over approximately 20 minutes on day 1 of every 21-day cycle.

Paclitaxel

Solution for infusion

Intravenous use

Participants received 175 mg/m^2 paclitaxel by IV infusion over approximately 3 hours on day 1 of every 21-day cycle.

Enfortumab Vedotin 1.25 mg/kg

Chemotherapy

Enfortumab Vedotin 1.25 mg/kg

Chemotherapy

OS was defined as the time from the date of randomization until the documented date of death from any cause. OS was analyzed using Kaplan-Meier estimates. Participants who were still alive at the time of data cutoff date were to be censored at the last known alive date or at the data cutoff date, whichever was earlier. The full analysis set (FAS) consisted of all participants who were randomized.

Primary

From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)

Enfortumab Vedotin 1.25 mg/kg v Chemotherapy

608

Pre-specified

0.702

2-sided

PFS: time from date of randomization until date of documented radiological disease progression (PD) per investigator based on RECIST V1.1, or until death due to any cause, whichever occurred first. PD: >= 20% increase in sum of diameters of target lesions taking as reference the smallest sum, and sum must also demonstrate an absolute increase of >= 5 mm. Appearance of 1 or more new lesions is also considered progression. A participant who neither progressed nor died was censored at date of last radiological assessment (RA)/ date of randomization if no post-baseline RA was available. Participants who received any further anticancer therapy (ACT) for disease before radiological progression was censored at date of last RA before ACT started and participants who had PD/death after >=2 missed RAs were censored at last RA prior to 2 or more missed RAs. Kaplan-Meier estimates was used. Median time of follow-up for PFS was based on data cut-off & is same as median follow-up time for OS. FAS.

Secondary

From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)

Enfortumab Vedotin 1.25 mg/kg v Chemotherapy

608

Pre-specified

0.615

2-sided

ORR was defined as the percentage of participants with complete response (CR) or partial response (PR) based on the 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. ORR was analysed using exact method based on binomial distribution (Clopper-Pearson). Median time of follow up for ORR was based on data cut-off and is same as median follow-up time for OS. Response Evaluable Set (RES): The RES was defined as all participants in the FAS who had measurable disease (per RECIST v1.1) per investigator at baseline.

Secondary

From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)

Enfortumab Vedotin 1.25 mg/kg v Chemotherapy

584

Pre-specified

DCR was defined as the percentage of participants with a CR, PR or a stable disease (SD) 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. Progressive disease is defined in PFS1 endpoint. DCR was analysed using exact method based on binomial distribution (Clopper-Pearson). Median time of follow up for DCR was based on data cut-off and is same as median follow-up time for OS. RES Population.

Secondary

From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)

Enfortumab Vedotin 1.25 mg/kg v Chemotherapy

584

Pre-specified

DOR: time from the date of the first CR/PR (whichever is first recorded) that was subsequently confirmed as assessed by investigator to the date of documented PD or death due to any cause whichever occurred first. If a participant has neither progressed nor died, the participant was censored at the date of last RA or at the date of first CR/PR if no subsequent post-baseline RA was available. Participants who received any further ACT for the disease before radiological progression were censored at the date of the last RA before the ACT started. In addition, participants who had PD/death after >= 2 missed RAs were censored at the last RA prior to the 2 or more missed RAs. Kaplan-Meier estimates was used. Median time of follow up for DOR was based on data cut-off and is same as median follow-up time for OS. RES population with available data. CR/PR and PD were defined in ORR and PFS1 endpoints, respectively.

Secondary

From date of first objective response until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)

EORTC QLQ-C30 is a generic questionnaire consisting of 30 items. The instrument yields functional scales (physical, role, emotional, cognitive, social), symptom scales/items (fatigue, Nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea), global health status, and financial impact score. Most items are scored 1 (“not at all”) to 4 (“very much”) except for the items contributing to the global health status/QoL, which are scored 1 (“very poor”) to 7 (“excellent”). The recall period for each question is “during the past week”. All raw domain scores are linearly transformed to a 0-100 scale with higher scores on symptoms indicate a worse health state. Higher scores on the global health status and functioning scales indicate better health status/function. FAS population with available data.

Secondary

Baseline and week 12

EQ-5D-5L is a health status instrument for self-reported assessment of 5 domains of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each domain is rated by selecting 1 of 5 standardized categorizations ranging from no problem to extreme problem. The final question is a visual analogue scale (VAS) to rank health status from 0 (best health imaginable) to 100 (worst health imaginable). FAS population with available data.

Secondary

Baseline and week 12

An AE is any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. A TEAE is defined as an AE observed or worsened after starting administration of the study drug. The safety analysis set (SAF) consisted of all participants who received any amount of study drug, and was used for safety analyses.

Secondary

From first dose up to 30 days after last dose (Median (range) time on study drug was 4.99 (0.5, 19.4) months in enfortumab vedotin and 3.45 (0.2, 15.0) months in chemotherapy group)

ECOG performance status was measured on an 6 point scale. 0-Fully active, able to carry on all pre-disease performance without restriction. 1-Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2-Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3-Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4-Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5-Dead. Number of participants with ECOG PS was reported. Safety population.

Secondary

From first dose up to 30 days after last dose (Median (range) time on study drug was 4.99 (0.5, 19.4) months in enfortumab vedotin and 3.45 (0.2, 15.0) months in chemotherapy group)

From first dose up to 30 days after last dose (Median (range) time on study drug was 4.99 (0.5, 19.4) months in enfortumab vedotin and 3.45 (0.2, 15.0) months in chemotherapy group)

v23.0

Enfortumab Vedotin 1.25 mg/kg

Chemotherapy