A Study to Evaluate Enfortumab Vedotin (ASG-22CE) in Chin... | NCT04995419

ID	Type	Description	Link
CTR20210922	Registry Identifier	chinadrugtrials.org.cn

Name	Class
Seagen Inc.	INDUSTRY

Label	Type	Description	Intervention Names
Enfortumab Vedotin 1.25 mg/kg	Experimental	Participants received 1.25 milligrams per kilogram (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. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first. Participants who had intense PK Sampling were enrolled in PK Cohort.	Drug: Enfortumab vedotin

Name	Type	Description	Arm Group Labels	Other Names
Enfortumab vedotin	Drug	Intravenous Infusion	Enfortumab Vedotin 1.25 mg/kg

Measure	Description	Time Frame
Objective Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors V1.1 (RECIST V1.1)	ORR was defined as the percentage of participants with best overall response (BOR) as 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.	From first dose up to progressive disease or death (maximum duration: 9.33 months)
Pharmacokinetics (PK) of Antibody-Drug Conjugate (ADC), Total Antibody (TAb), in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 1	Cmax was derived from the PK blood samples collected.	Cycle 1 Day 1: pre-dose, end of infusion (EOI), 2 hour, 4 hour post-dose (each cycle = 28 days)
PK of Monomethyl Auristatin E (MMAE) in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 1	Cmax was derived from the PK blood samples collected.	Cycle 1 Day 1: pre-dose, end of infusion (EOI), 2 hour, 4 hour post-dose (each cycle = 28 days)
PK of ADC, TAb in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 15	Cmax was derived from the PK blood samples collected.	Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
PK of MMAE in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 15	Cmax was derived from the PK blood samples collected.	Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

Measure	Description	Time Frame
Duration of Response (DOR) as Per RECIST V1.1 Per IRC	DOR: time from the date of the first CR/PR (whichever is first recorded) that was subsequently confirmed as assessed by IRC to the date of documented progressive disease. or death due to any cause whichever occurred first. 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. Progressive Disease:>= 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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Participant has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Participant must have histologically or cytologically documented urothelial/transitional cell carcinoma of the bladder, renal pelvis, ureter or urethra. Other histologies including adenocarcinoma, squamous differentiation or mixed are eligible.
Participant has locally advanced or metastatic disease that is not amenable to curative intent treatment. Participants must have measurable disease at baseline according to Response Evaluation Criteria in Solid Tumors (RECIST) ( Version 1.1). Lesions in a prior radiation field must have progressed subsequent to radiotherapy to be considered measurable.
Participant must have received prior treatment with PD-1/PD-L1 inhibitor therapy in the locally advanced or metastatic urothelial cancer setting. Participants who received PD-1/PD-L1 therapy in the neoadjuvant/adjuvant setting and had recurrent or progressive disease either during therapy or within 3 months of therapy completion are eligible.
Participant who received prior treatment with platinum-containing chemotherapy defined as those who received platinum in the neoadjuvant/adjuvant setting and had recurrent or progressive disease within 12 months of completion or received treatment with platinum in the locally advanced (defined as unresectable with curative intent) or metastatic setting.
- Platinum based chemotherapy may include combination use with a PD-1 or PD-L1 inhibitor.
Participant has the following baseline laboratory data. If a participant has received a recent blood transfusion or growth factor, the hematology tests must be obtained ≥7 days after any growth factor and ≥ 28 days after any blood transfusion.
- absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L
- platelet count ≥ 100 × 10^9/L
- hemoglobin ≥ 9 g/dL
- serum total bilirubin (TBL) ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for participants with Gilbert's disease
- creatinine clearance (CrCl) ≥ 30 mL/min as estimated per institutional standards or as measured by 24-hour urine collection (glomerular filtration rate [GFR] can also be used instead of CrCl).
- alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN
Female participant is not pregnant and at least one of the following conditions apply:
- Not a woman of childbearing potential (WOCBP)
- WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 6 months after the last dose of study treatment administration.
Female participant must agree not to breastfeed starting at screening and throughout the study period and for at least 6 months after the last dose of study treatment administration.
Female participant must not donate ova starting at first dose of study treatment and throughout the study period and for 6 months after the last dose of study treatment administration.
Male participant with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the treatment period and for 6 months after the last dose of study treatment administration.
Male participant must not donate sperm during the treatment period and for 6 months after the last dose of study treatment administration.
Male participant with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 6 months after the last dose of study treatment administration.
Participant agrees not to participate in another interventional study while receiving study treatment in the present study.
Participant must have had progression or recurrence of urothelial cancer during or following receipt of most recent therapy.
Participant must have an anticipated life expectancy of ≥ 3 months.

Exclusion Criteria:

Participant has preexisting sensory or motor neuropathy Grade ≥ 2.
Participant has active central nervous system (CNS) metastases. Participants with treated CNS metastases are permitted on study if all the following are true:
- CNS metastases have been clinically stable for ≥ 6 weeks prior to screening.
- If requiring steroid treatment for CNS metastases, the participant is on a stable dose ≤ 20 mg/day of prednisone or equivalent for ≥ 2 weeks.
- Baseline imaging scans show no evidence of new or enlarged brain metastasis.
- Participant does not have leptomeningeal disease.
Participant has ongoing clinically significant toxicity (Grade 2 or higher with the exception of alopecia) associated with prior treatment (including systemic therapy, radiotherapy or surgery).
Participant with ongoing ≥ Grade 3 immunotherapy-related hypothyroidism or panhypopituitarism is excluded. Participant with ongoing immunotherapy-related colitis, uveitis, myocarditis or pneumonitis, or participants with other immunotherapy-related AEs requiring high doses of steroids (> 20 mg/day of prednisone or equivalent), is excluded. Participant with ≤ Grade 2 immunotherapy-related hypothyroidism or panhypopituitarism may be enrolled when well-maintained/controlled on a stable dose of hormone replacement therapy (if indicated).
Participant has a history of uncontrolled diabetes mellitus within 3 months before the first dose of study treatment. Uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) ≥ 8 percent or HbA1c between 7 percent and < 8 percent with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
Participant has prior treatment with enfortumab vedotin or other monomethyl auristatin E (MMAE)-based antibody-drug conjugate (ADCs).
Participant has a second malignancy diagnosed within 3 years before first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Participants with non-melanoma skin cancer, localized prostate cancer treated with curative intent with no evidence of progression, low-risk or very low-risk (per standard guidelines) localized prostate cancer under active surveillance/watchful waiting without intent to treat, or carcinoma in situ of any type (if complete resection was performed) are allowed.
Participant is currently receiving systemic antimicrobial treatment for viral, bacterial or fungal infection at the time of first dose of study treatment. Routine antimicrobial prophylaxis is permitted.
Participants with a positive hepatitis B surface antigen and/or anti-hepatitis B core antibody and a negative polymerase chain reaction (PCR) assay at baseline should receive appropriate antiviral prophylaxis or regular surveillance monitoring as per local or institutional guidelines.
Active hepatitis C infection or known human immunodeficiency virus (HIV) infection. Participant who have been treated for hepatitis C infection are permitted if they have documented sustained virologic response of ≥ 12 weeks.
Participant has documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction or cardiac symptoms (including congestive heart failure) consistent with New York Heart Association Class III-IV within 6 months prior to the first dose of study drug.
Participant had major surgery within 2 weeks or radiotherapy, chemotherapy, biologics, investigational agents, and/or antitumor treatment with immunotherapy that is not completed 2 weeks prior to first dose of study drug. Toxicities from these therapies must have resolved or adequately stabilized before starting study treatment.
Participant has known hypersensitivity to enfortumab vedotin or to any excipient contained in the drug formulation of enfortumab vedotin (including histidine, trehalose dihydrate and polysorbate 20) or participant has known hypersensitivity to biopharmaceuticals produced in CHO cells.
Participant has known active keratitis or corneal ulcerations. Participant with superficial punctate keratitis is allowed if the disorder is being adequately treated.
Participant has any condition which makes the participant unsuitable for study participation.
Uncontrolled tumor-related bone pain or impending spinal cord compression. Participant requiring pain medication must be on a stable regimen for at least 2 weeks at the time of first dose.

Name	Affiliation	Role
Senior Medical Science Manager	Astellas Pharma China, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Site CN86001		Beijing			China
Site CN86009

PubMed Identifier	Type	Citation	Retractions
39530574	Derived	Li S, Shi Y, Dong H, Guo H, Xie Y, Sun Z, Zhang X, Kim E, Zhang J, Li Y, Xu C, Kadeerbai H, Lee S, Gorla S, Guo J, Sheng X. Phase 2 Trial of Enfortumab Vedotin in Patients With Previously Treated Locally Advanced or Metastatic Urothelial Carcinoma in China. Cancer Med. 2024 Nov;13(21):e70368. doi: 10.1002/cam4.70368.

ID	Title	Description
FG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 milligrams per kilogram (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. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 29, 2022	May 10, 2023

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Objective Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors V1.1 (RECIST V1.1)

ORR was defined as the percentage of participants with best overall response (BOR) as 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.

FAS population

Posted

Number

95% Confidence Interval

percentage of participants

From first dose up to progressive disease or death (maximum duration: 9.33 months)

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Units	Counts
Participants	OG00040

Title

Denominators

Categories

Title	Measurements
	OG00037.5(22.7 to 54.2)

Primary

Pharmacokinetics (PK) of Antibody-Drug Conjugate (ADC), Total Antibody (TAb), in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 1

Cmax was derived from the PK blood samples collected.

Pharmacokinetic Analysis Set (PKAS) included all participants in the PK cohort who had received at least 3 of 4 doses up through Cycle 2 Day 1, and had at least 5 blood samples collected and assayed for measurement of ADC, TAb or unconjugated MMAE serum/plasma concentrations to determine at least 1 PK parameter.

Posted

Mean

Standard Deviation

micrograms per milliliter (ug/mL)

Cycle 1 Day 1: pre-dose, end of infusion (EOI), 2 hour, 4 hour post-dose (each cycle = 28 days)

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Units	Counts
Participants	OG000

Primary

PK of Monomethyl Auristatin E (MMAE) in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 1

Cmax was derived from the PK blood samples collected.

PKAS population.

Posted

Mean

Standard Deviation

nanograms per milliliter (ng/mL)

Cycle 1 Day 1: pre-dose, end of infusion (EOI), 2 hour, 4 hour post-dose (each cycle = 28 days)

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Units	Counts
Participants	OG000

Primary

PK of ADC, TAb in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 15

Cmax was derived from the PK blood samples collected.

PKAS population with available data were analyzed.

Posted

Mean

Standard Deviation

ug/mL

Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Units	Counts
Participants	OG000

Primary

PK of MMAE in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 15

Cmax was derived from the PK blood samples collected.

PKAS population with available data were analyzed.

Posted

Mean

Standard Deviation

ng/mL

Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Units	Counts
Participants	OG000

Primary

PK of ADC , TAb in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 1

As per planned analysis, if more than 50% of PK concentrations were below the limit of quantification (i.e 0) at a given time point, standard deviation was not reported.

PKAS population.

Posted

Mean

Standard Deviation

ug/mL

Cycle 1 Day 1: pre-dose

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Units	Counts
Participants	OG000

Primary

PK of MMAE in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 1

As per planned analysis, if more than 50% of PK concentrations were below the limit of quantification (i.e 0) at a given time point, standard deviation was not reported.

PKAS population.

Posted

Mean

Standard Deviation

ng/mL

Cycle 1 Day 1: pre-dose

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Units	Counts
Participants	OG000

Primary

PK of ADC, TAb in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 15

Ctrough was derived from the PK blood samples collected.

PKAS population with available data were analyzed.

Posted

Mean

Standard Deviation

ug/mL

Cycle 1 Day 15: pre-dose

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Units	Counts
Participants	OG000

Primary

PK of MMAE in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 15

Ctrough was derived from the PK blood samples collected.

PKAS population with available data were analyzed.

Posted

Mean

Standard Deviation

picograms per milliliter (pg/mL)

Cycle 1 Day 15: pre-dose

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Units	Counts
Participants	OG000

Primary

PK of ADC, TAb, MMAE in Serum: Time to Maximum Concentration (Tmax) at Cycle 1 Day 1

Tmax was derived from the PK blood samples collected.

PKAS population.

Posted

Median

Full Range

days

Cycle 1 Day 1: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Units	Counts
Participants	OG000

Primary

PK of ADC, TAb, MMAE in Serum: Time to Maximum Concentration (Tmax) at Cycle 1 Day 15

Tmax was derived from the PK blood samples collected.

PKAS population with available data were analyzed.

Posted

Median

Full Range

days

Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Units	Counts
Participants	OG000

Primary

PK of ADC, TAb, MMAE in Serum: Area Under Concentration-time Curve From 0 to Day 28 (AUC0-28d) at Cycle 1 Day 1

AUC0-28d was derived from the PK blood samples collected.

Per protocol, data for AUC0-28d was planned to be calculated using non-compartment analysis (NCA) only if data permits, therefore AUC 0-28d was removed from the planned analysis in SAP.

Posted

Cycle 1 Day 1: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Units	Counts
Participants	OG000

Primary

PK of ADC, TAb, MMAE in Serum: Area Under Concentration-time Curve From 0 to Day 28 (AUC0-28d) at Cycle 1 Day 15

AUC0-28d was derived from the PK blood samples collected.

Per protocol, data for AUC0-28d was planned to be calculated using non-compartment analysis (NCA) only if data permits, therefore AUC 0-28d was removed from the planned analysis in SAP.

Posted

Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Units	Counts
Participants	OG000

Primary

PK of ADC, TAb in Serum: Area Under Concentration-time Curve From 0 to Day 7 (AUC0-7d) at Cycle 1 Day 1

AUC0-7d was derived from the PK blood samples collected.

PKAS population with available data were analyzed.

Posted

Mean

Standard Deviation

day*ug/mL

Cycle 1 Day 1 : pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Units	Counts
Participants	OG000

Primary

PK of MMAE in Serum: Area Under Concentration-time Curve From 0 to Day 7 (AUC0-7d) at Cycle 1 Day 1

AUC0-7d was derived from the PK blood samples collected.

PKAS population with available data were analyzed.

Posted

Mean

Standard Deviation

day*ng/mL

Cycle 1 Day 1 : pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Units	Counts
Participants	OG000

Primary

PK of ADC, TAb in Serum: Area Under Concentration-time Curve From 0 to Day 7 (AUC0-7d) at Cycle 1 Day 15

AUC0-7d was derived from the PK blood samples collected.

PKAS population with available data were analyzed.

Posted

Mean

Standard Deviation

day*ug/mL

Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Units	Counts
Participants	OG000

Primary

PK of MMAE in Serum: Area Under Concentration-time Curve From 0 to Day 7 (AUC0-7d) at Cycle 1 Day 15

AUC0-7d was derived from the PK blood samples collected.

PKAS population with available data were analyzed.

Posted

Mean

Standard Deviation

day*ng/mL

Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Units	Counts
Participants	OG000

Primary

PK of ADC, TAb, MMAE in Plasma: Accumulation Ratio of Cmax (RacCmax)

Accumulation ratio is the ratio of Cmax after the dosing interval (Cycle 1 Day 15) divided by Cmax after the first dosing interval (Cycle 1 Day 1).

PKAS population with available data were analyzed.

Posted

Mean

Standard Deviation

ratio

Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Units	Counts
Participants	OG000

Primary

PK of ADC, TAb, MMAE in Serum: Accumulation Ratio of AUC0-7d ( RacAUC0-7d)

RacAUC0-7d was calculated using AUC0-7d and derived from the PK blood samples collected.

PKAS population with available data were analyzed.

Posted

Mean

Standard Deviation

ratio

Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Units	Counts
Participants	OG000

Primary

PK of ADC, TAb, MMAE in Serum: Terminal Elimination Half-life (t1/2)

t1/2 was derived from the PK blood samples collected.

PKAS population with available data were analyzed.

Posted

Median

Full Range

days

Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Units	Counts
Participants	OG000

Primary

PK of ADC, TAb, MMAE in Serum: Systemic Clearance (CL)

CL was derived from the PK blood samples collected.

PKAS population with available data were analyzed.

Posted

Mean

Standard Deviation

Liters/hour (L/hr)

Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Units	Counts
Participants	OG000

Primary

PK of ADC, TAb, MMAE in Serum: Volume of Distribution at Steady State (Vss)

Vss was derived from the PK blood samples collected.

PKAS population with available data were analyzed.

Posted

Mean

Standard Deviation

Liters

Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Units	Counts
Participants	OG000

Secondary

Duration of Response (DOR) as Per RECIST V1.1 Per IRC

DOR: time from the date of the first CR/PR (whichever is first recorded) that was subsequently confirmed as assessed by IRC to the date of documented progressive disease. or death due to any cause whichever occurred first. 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. Progressive Disease:>= 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.

FAS population with available data were analyzed.

Posted

Median

95% Confidence Interval

months

From date of the first CR/PR up to progressive disease or death (maximum duration: 9.33 months)

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Secondary

Duration of Response (DOR) as Per RECIST V1.1 Per Investigator's Assessment

DOR: time from the date of the first CR/PR (whichever is first recorded) that was subsequently confirmed as assessed by Investigator's Assesment to the date of documented progressive disease or death due to any cause whichever occurred first. 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. Progressive disease:>= 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.

FAS population with available data were analyzed.

Posted

Median

95% Confidence Interval

months

From date of the first CR/PR up to progressive disease or death (maximum duration: 9.33 months)

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Secondary

Objective Response Rate (ORR) as Per Investigator Assessment

ORR was defined as the percentage of participants with BOR as CR or PR based on the RECIST v1.1 as per investigator's assesment. 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.

FAS population

Posted

Number

95% Confidence Interval

percentage of participants

From first dose up to progressive disease or death (maximum duration: 9.33 months)

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Units	Counts
Participants

Secondary

Disease Control Rate (DCR) as Per RECIST V1.1 Per IRC

DCR: percentage of participants with a CR, PR or SD based on RECIST v1.1 as assessed by IRC. 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:>= 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.

FAS population.

Posted

Number

95% Confidence Interval

percentage of participants

From first dose up to progressive disease or death (maximum duration: 9.33 months)

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Secondary

Disease Control Rate (DCR) as Per RECIST V1.1 Per Investigator's Assesment

DCR: percentage of participants with a CR, PR or SD based on RECIST v1.1 as assessed by investigator's assessment. 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:>= 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.

FAS population.

Posted

Number

95% Confidence Interval

percentage of participants

From first dose up to progressive disease or death (maximum duration: 9.33 months)

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Secondary

Progression Free-Survival Per RECIST V1.1 Per IRC

PFS: time from first dose of the study drug until date of documented radiological disease progression per IRC based on RECIST V1.1, or until death due to any cause, whichever occurred first. Progressive disease: >= 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.

FAS population

Posted

Median

95% Confidence Interval

months

From first dose up to progressive disease or death (maximum duration: 9.33 months)

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Secondary

Progression Free-Survival Per RECIST V1.1 Per Investigator's Assessment

PFS: time from first dose of the study drug until date of documented radiological disease progression per investigator based on RECIST V1.1, or until death due to any cause, whichever occurred first. Progressive disease: >= 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 RA/ date of randomization if no post-baseline RA was available. Participants who received any further ACT for disease before radiological progression was censored at date of last RA before ACT started and participants who had progressive disease/death after >=2 missed RAs were censored at last RA prior to 2 or more missed RAs. Kaplan-Meier estimates was used.

FAS population

Posted

Median

95% Confidence Interval

months

From first dose up to progressive disease or death (maximum duration: 9.33 months)

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Secondary

Overall Survival (OS)

OS was defined as the time from first dose of the study drug 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.

FAS population

Posted

Median

95% Confidence Interval

months

From first dose up to death (maximum duration: 9.33 months)

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Antitherapeutic Antibodies (ATA)

Number of participants with ATA were reported.

FAS population with available data were analyzed.

Posted

Count of Participants

Participants

From first dose until 9.33 months

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Treatment Emergent Adverse Events

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. TEAE is defined as an adverse event observed after starting administration of the study drug and within 30 days after taking the last dose of study drug.

Safety analysis set (SAF) included all participants who were enrolled and received any amount of study drug in the study.

Posted

Count of Participants

Participants

Baseline up to 9.33 months

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Units	Counts
Participants

Secondary

Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)

ECOG performance status was measured on an 6 point scale. 0-Fully active, able to carry on all pre-disease performance without restriction.

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.
Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
Dead. Number of participants with ECOG PS was reported."

SAF population

Posted

Count of Participants

Participants

End of Treatment (Baseline up to 9.33 months)

ID	Title	Description
OG000	Enfortumab Vedotin 1.25 mg/kg	Participants received 1.25 mg/kg of body weight enfortumab vedotin by IV infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.

Units	Counts
Participants

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA v24.0	Systematic Assessment	EG00081 events28 affected40 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected40 at risk
Sinus tachycardia	Cardiac disorders	MedDRA v24.0	Systematic Assessment	EG0006 events4 affected40 at risk
Dry eye	Eye disorders	MedDRA v24.0	Systematic Assessment	EG0003 events3 affected40 at risk
Eye discharge	Eye disorders	MedDRA v24.0	Systematic Assessment	EG0005 events5 affected40 at risk
Vision blurred	Eye disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected40 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0004 events4 affected40 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0005 events4 affected40 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0005 events5 affected40 at risk
Constipation	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG00025 events19 affected40 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG00031 events19 affected40 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG00010 events7 affected40 at risk
Dysphagia	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG00010 events6 affected40 at risk
Flatulence	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected40 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0005 events4 affected40 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected40 at risk
Mouth ulceration	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0007 events7 affected40 at risk
Nausea	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG00039 events20 affected40 at risk
Stomatitis	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected40 at risk
Vomiting	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG00017 events12 affected40 at risk
Asthenia	General disorders	MedDRA v24.0	Systematic Assessment	EG0004 events4 affected40 at risk
Fatigue	General disorders	MedDRA v24.0	Systematic Assessment	EG00031 events10 affected40 at risk
Malaise	General disorders	MedDRA v24.0	Systematic Assessment	EG0007 events6 affected40 at risk
Oedema peripheral	General disorders	MedDRA v24.0	Systematic Assessment	EG00015 events7 affected40 at risk
Pyrexia	General disorders	MedDRA v24.0	Systematic Assessment	EG00017 events14 affected40 at risk
Herpes dermatitis	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected40 at risk
Herpes virus infection	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected40 at risk
Pneumonia	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0004 events3 affected40 at risk
Skin infection	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0008 events6 affected40 at risk
Urinary tract infection	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0003 events3 affected40 at risk
Alanine aminotransferase increased	Investigations	MedDRA v24.0	Systematic Assessment	EG00030 events18 affected40 at risk
Aspartate aminotransferase increased	Investigations	MedDRA v24.0	Systematic Assessment	EG00043 events26 affected40 at risk
Bilirubin conjugated increased	Investigations	MedDRA v24.0	Systematic Assessment	EG0008 events2 affected40 at risk
Blood bilirubin increased	Investigations	MedDRA v24.0	Systematic Assessment	EG00018 events4 affected40 at risk
Blood bilirubin unconjugated increased	Investigations	MedDRA v24.0	Systematic Assessment	EG0003 events2 affected40 at risk
Blood creatinine increased	Investigations	MedDRA v24.0	Systematic Assessment	EG0007 events5 affected40 at risk
Blood glucose increased	Investigations	MedDRA v24.0	Systematic Assessment	EG0005 events4 affected40 at risk
Blood lactate dehydrogenase increased	Investigations	MedDRA v24.0	Systematic Assessment	EG0003 events2 affected40 at risk
Blood triglycerides increased	Investigations	MedDRA v24.0	Systematic Assessment	EG0003 events2 affected40 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA v24.0	Systematic Assessment	EG0005 events3 affected40 at risk
Glycosylated haemoglobin increased	Investigations	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected40 at risk
Lymphocyte count decreased	Investigations	MedDRA v24.0	Systematic Assessment	EG0006 events3 affected40 at risk
Neutrophil count decreased	Investigations	MedDRA v24.0	Systematic Assessment	EG00036 events19 affected40 at risk
Occult blood positive	Investigations	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected40 at risk
Platelet count decreased	Investigations	MedDRA v24.0	Systematic Assessment	EG00022 events9 affected40 at risk
Weight decreased	Investigations	MedDRA v24.0	Systematic Assessment	EG00017 events10 affected40 at risk
White blood cell count decreased	Investigations	MedDRA v24.0	Systematic Assessment	EG00043 events16 affected40 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG00046 events26 affected40 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG00020 events5 affected40 at risk
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG0006 events4 affected40 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG00057 events20 affected40 at risk
Hyperlipidaemia	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected40 at risk
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG00017 events6 affected40 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG00024 events11 affected40 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG00022 events10 affected40 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG00022 events8 affected40 at risk
Hypochloraemia	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG0009 events5 affected40 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG0004 events2 affected40 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG00028 events15 affected40 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG00035 events13 affected40 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG00014 events7 affected40 at risk
Hypoproteinaemia	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG0003 events2 affected40 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA v24.0	Systematic Assessment	EG0004 events4 affected40 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA v24.0	Systematic Assessment	EG0005 events4 affected40 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected40 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected40 at risk
Dizziness	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0003 events3 affected40 at risk
Dysgeusia	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG00021 events10 affected40 at risk
Hypoaesthesia	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0007 events6 affected40 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0009 events8 affected40 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected40 at risk
Insomnia	Psychiatric disorders	MedDRA v24.0	Systematic Assessment	EG00015 events8 affected40 at risk
Dysuria	Renal and urinary disorders	MedDRA v24.0	Systematic Assessment	EG0003 events3 affected40 at risk
Haematuria	Renal and urinary disorders	MedDRA v24.0	Systematic Assessment	EG0005 events3 affected40 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA v24.0	Systematic Assessment	EG00012 events8 affected40 at risk
Dry throat	Respiratory, thoracic and mediastinal disorders	MedDRA v24.0	Systematic Assessment	EG0004 events4 affected40 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected40 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected40 at risk
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA v24.0	Systematic Assessment	EG0003 events2 affected40 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA v24.0	Systematic Assessment	EG0004 events3 affected40 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected40 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA v24.0	Systematic Assessment	EG0006 events4 affected40 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG00017 events12 affected40 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected40 at risk
Drug eruption	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG0008 events4 affected40 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG0005 events3 affected40 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected40 at risk
Papule	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG0005 events5 affected40 at risk
Pigmentation disorder	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG0008 events8 affected40 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG00027 events14 affected40 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG00056 events17 affected40 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG00013 events6 affected40 at risk
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG0005 events5 affected40 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG0005 events3 affected40 at risk
Hypotension	Vascular disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected40 at risk