Metastatic Urothelial Cancer
Conditions
Keywords
Enfortumab Vedotin, PADCEV, ASG-22CE, Pharmacokinetics, Urothelial cancer
Brief summary
The purpose of this study was to determine the antitumor activity of enfortumab vedotin (EV) confirmed by the objective response rate (ORR). This study also evaluated the effect of antibody-drug conjugate (ADC), total antibody (TAb) and monomethyl auristatin E (MMAE) in Chinese participants with locally advanced or metastatic urothelial cancer. In addition, the study also evaluated the duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and immunogenicity determined by the incidence of antitherapeutic antibodies (ATA). Safety and tolerability of EV in participants with locally advanced or metastatic urothelial cancer was also evaluated.
Detailed description
This study comprised of a single group of participants who received one dose of enfortumab vedotin (EV) on Days 1, 8 and 15 of every 4-week (28 days) cycle. Participants continued on study treatment until discontinuation. After treatment discontinuation, participant had an end of treatment (EOT) visit for a 30-day Safety Follow-up. Participants to discontinue to treatment for reasons other than disease progression were followed for response assessments. A Pharmacokinetic (PK) cohort was available at some study centers. Participants enrolled at the PK cohort site(s) had intense PK samples collected after single and repeated doses.
Interventions
DRUGEnfortumab vedotin
Intravenous Infusion
Sponsors
Seagen Inc.
Astellas Pharma China, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK of ADC, TAb, MMAE in Serum: Volume of Distribution at Steady State (Vss) | Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days) | Vss was derived from the PK blood samples collected. |
| PK of ADC, TAb, MMAE in Serum: Time to Maximum Concentration (Tmax) at Cycle 1 Day 15 | Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days) | Tmax was derived from the PK blood samples collected. |
| PK of ADC, TAb, MMAE in Serum: Area Under Concentration-time Curve From 0 to Day 28 (AUC0-28d) at Cycle 1 Day 1 | Cycle 1 Day 1: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days) | AUC0-28d was derived from the PK blood samples collected. |
| PK of ADC, TAb, MMAE in Serum: Area Under Concentration-time Curve From 0 to Day 28 (AUC0-28d) at Cycle 1 Day 15 | Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days) | AUC0-28d was derived from the PK blood samples collected. |
| PK of ADC, TAb in Serum: Area Under Concentration-time Curve From 0 to Day 7 (AUC0-7d) at Cycle 1 Day 1 | Cycle 1 Day 1 : pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days) | AUC0-7d was derived from the PK blood samples collected. |
| PK of MMAE in Serum: Area Under Concentration-time Curve From 0 to Day 7 (AUC0-7d) at Cycle 1 Day 1 | Cycle 1 Day 1 : pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days) | AUC0-7d was derived from the PK blood samples collected. |
| PK of ADC, TAb in Serum: Area Under Concentration-time Curve From 0 to Day 7 (AUC0-7d) at Cycle 1 Day 15 | Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days) | AUC0-7d was derived from the PK blood samples collected. |
| PK of MMAE in Serum: Area Under Concentration-time Curve From 0 to Day 7 (AUC0-7d) at Cycle 1 Day 15 | Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days) | AUC0-7d was derived from the PK blood samples collected. |
| PK of ADC, TAb, MMAE in Plasma: Accumulation Ratio of Cmax (RacCmax) | Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days) | 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). |
| PK of ADC, TAb, MMAE in Serum: Accumulation Ratio of AUC0-7d ( RacAUC0-7d) | Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days) | RacAUC0-7d was calculated using AUC0-7d and derived from the PK blood samples collected. |
| PK of ADC, TAb, MMAE in Serum: Terminal Elimination Half-life (t1/2) | Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days) | t1/2 was derived from the PK blood samples collected. |
| PK of ADC, TAb, MMAE in Serum: Systemic Clearance (CL) | Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days) | CL was derived from the PK blood samples collected. |
| PK of ADC, TAb in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 15 | Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days) | Cmax was derived from the PK blood samples collected. |
| Objective Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors V1.1 (RECIST V1.1) | From first dose up to progressive disease or death (maximum duration: 9.33 months) | 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. |
| Pharmacokinetics (PK) of Antibody-Drug Conjugate (ADC), Total Antibody (TAb), in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 1 | Cycle 1 Day 1: pre-dose, end of infusion (EOI), 2 hour, 4 hour post-dose (each cycle = 28 days) | Cmax was derived from the PK blood samples collected. |
| PK of Monomethyl Auristatin E (MMAE) in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 1 | Cycle 1 Day 1: pre-dose, end of infusion (EOI), 2 hour, 4 hour post-dose (each cycle = 28 days) | Cmax was derived from the PK blood samples collected. |
| PK of MMAE in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 15 | Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days) | Cmax was derived from the PK blood samples collected. |
| PK of ADC , TAb in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 1 | Cycle 1 Day 1: pre-dose | 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. |
| PK of MMAE in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 1 | Cycle 1 Day 1: pre-dose | 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. |
| PK of ADC, TAb in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 15 | Cycle 1 Day 15: pre-dose | Ctrough was derived from the PK blood samples collected. |
| PK of MMAE in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 15 | Cycle 1 Day 15: pre-dose | Ctrough was derived from the PK blood samples collected. |
| PK of ADC, TAb, MMAE in Serum: Time to Maximum Concentration (Tmax) at Cycle 1 Day 1 | Cycle 1 Day 1: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days) | Tmax was derived from the PK blood samples collected. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) as Per RECIST V1.1 Per Investigator's Assessment | From date of the first CR/PR up to progressive disease or death (maximum duration: 9.33 months) | 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. |
| Objective Response Rate (ORR) as Per Investigator Assessment | From first dose up to progressive disease or death (maximum duration: 9.33 months) | 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. |
| Disease Control Rate (DCR) as Per RECIST V1.1 Per IRC | From first dose up to progressive disease or death (maximum duration: 9.33 months) | 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. |
| Disease Control Rate (DCR) as Per RECIST V1.1 Per Investigator's Assesment | From first dose up to progressive disease or death (maximum duration: 9.33 months) | 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. |
| Progression Free-Survival Per RECIST V1.1 Per IRC | From first dose up to progressive disease or death (maximum duration: 9.33 months) | 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. |
| Progression Free-Survival Per RECIST V1.1 Per Investigator's Assessment | From first dose up to progressive disease or death (maximum duration: 9.33 months) | 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. |
| Overall Survival (OS) | From first dose up to death (maximum duration: 9.33 months) | 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. |
| Number of Participants With Antitherapeutic Antibodies (ATA) | From first dose until 9.33 months | Number of participants with ATA were reported. |
| Number of Participants With Treatment Emergent Adverse Events | Baseline up to 9.33 months | 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. |
| Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) | End of Treatment (Baseline up to 9.33 months) | 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. |
| Duration of Response (DOR) as Per RECIST V1.1 Per IRC | From date of the first CR/PR up to progressive disease or death (maximum duration: 9.33 months) | 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. |
Countries
China
Participant flow
Recruitment details
Adult Chinese participants with locally advanced or metastatic urothelial cancer (mUC) who had received a platinum-containing chemotherapy and programmed cell death protein-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors.
Pre-assignment details
Participants who met inclusion criteria and none of the exclusion criteria were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Ongoing | 16 |
| Overall Study | Progressive Disease | 19 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Enfortumab Vedotin 1.25 mg/kg |
|---|---|
| Age, Continuous | 60.3 years STANDARD_DEVIATION 8.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 40 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 10 / 40 |
| other Total, other adverse events | 40 / 40 |
| serious Total, serious adverse events | 18 / 40 |
Outcome results
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.
Time frame: From first dose up to progressive disease or death (maximum duration: 9.33 months)
Population: FAS population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | Objective Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors V1.1 (RECIST V1.1) | 37.5 percentage of participants |
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.
Time frame: Cycle 1 Day 1: pre-dose, end of infusion (EOI), 2 hour, 4 hour post-dose (each cycle = 28 days)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | Pharmacokinetics (PK) of Antibody-Drug Conjugate (ADC), Total Antibody (TAb), in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 1 | ADC | 28.1 micrograms per milliliter (ug/mL) | Standard Deviation 4.52 |
| Enfortumab Vedotin 1.25 mg/kg | Pharmacokinetics (PK) of Antibody-Drug Conjugate (ADC), Total Antibody (TAb), in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 1 | TAb | 31.7 micrograms per milliliter (ug/mL) | Standard Deviation 5.73 |
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.
Time frame: Cycle 1 Day 1 : pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
Population: PKAS population with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb in Serum: Area Under Concentration-time Curve From 0 to Day 7 (AUC0-7d) at Cycle 1 Day 1 | ADC | 32.4 day*ug/mL | Standard Deviation 6.24 |
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb in Serum: Area Under Concentration-time Curve From 0 to Day 7 (AUC0-7d) at Cycle 1 Day 1 | TAb | 77.4 day*ug/mL | Standard Deviation 17.3 |
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.
Time frame: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
Population: PKAS population with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb in Serum: Area Under Concentration-time Curve From 0 to Day 7 (AUC0-7d) at Cycle 1 Day 15 | ADC | 36.5 day*ug/mL | Standard Deviation 7.93 |
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb in Serum: Area Under Concentration-time Curve From 0 to Day 7 (AUC0-7d) at Cycle 1 Day 15 | TAb | 94.7 day*ug/mL | Standard Deviation 15.7 |
Primary
PK of ADC, TAb in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 15
Cmax was derived from the PK blood samples collected.
Time frame: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
Population: PKAS population with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 15 | ADC | 27.6 ug/mL | Standard Deviation 4.01 |
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 15 | TAb | 34.4 ug/mL | Standard Deviation 4.64 |
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.
Time frame: Cycle 1 Day 1: pre-dose
Population: PKAS population.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC , TAb in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 1 | TAb | 0 ug/mL |
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC , TAb in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 1 | ADC | 0 ug/mL |
Primary
PK of ADC, TAb in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 15
Ctrough was derived from the PK blood samples collected.
Time frame: Cycle 1 Day 15: pre-dose
Population: PKAS population with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 15 | ADC | 1020 ug/mL | Standard Deviation 410 |
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 15 | TAb | 4620 ug/mL | Standard Deviation 1590 |
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).
Time frame: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
Population: PKAS population with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb, MMAE in Plasma: Accumulation Ratio of Cmax (RacCmax) | ADC | 1.03 ratio | Standard Deviation 0.15 |
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb, MMAE in Plasma: Accumulation Ratio of Cmax (RacCmax) | TAb | 1.13 ratio | Standard Deviation 0.137 |
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb, MMAE in Plasma: Accumulation Ratio of Cmax (RacCmax) | MMAE | 1.28 ratio | Standard Deviation 0.499 |
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.
Time frame: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
Population: PKAS population with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb, MMAE in Serum: Accumulation Ratio of AUC0-7d ( RacAUC0-7d) | TAb | 1.29 ratio | Standard Deviation 0.208 |
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb, MMAE in Serum: Accumulation Ratio of AUC0-7d ( RacAUC0-7d) | MMAE | 1.32 ratio | Standard Deviation 0.486 |
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb, MMAE in Serum: Accumulation Ratio of AUC0-7d ( RacAUC0-7d) | ADC | 1.20 ratio | Standard Deviation 0.228 |
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.
Time frame: Cycle 1 Day 1: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
Population: 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.
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.
Time frame: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
Population: 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.
Primary
PK of ADC, TAb, MMAE in Serum: Systemic Clearance (CL)
CL was derived from the PK blood samples collected.
Time frame: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
Population: PKAS population with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb, MMAE in Serum: Systemic Clearance (CL) | ADC | 0.104 Liters/hour (L/hr) | Standard Deviation 0.0239 |
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb, MMAE in Serum: Systemic Clearance (CL) | TAb | 0.0396 Liters/hour (L/hr) | Standard Deviation 0.00847 |
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb, MMAE in Serum: Systemic Clearance (CL) | MMAE | 196 Liters/hour (L/hr) | Standard Deviation 76.2 |
Primary
PK of ADC, TAb, MMAE in Serum: Terminal Elimination Half-life (t1/2)
t1/2 was derived from the PK blood samples collected.
Time frame: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
Population: PKAS population with available data were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb, MMAE in Serum: Terminal Elimination Half-life (t1/2) | ADC | 2.81 days |
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb, MMAE in Serum: Terminal Elimination Half-life (t1/2) | TAb | 3.82 days |
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb, MMAE in Serum: Terminal Elimination Half-life (t1/2) | MMAE | 3.12 days |
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.
Time frame: Cycle 1 Day 1: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
Population: PKAS population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb, MMAE in Serum: Time to Maximum Concentration (Tmax) at Cycle 1 Day 1 | MMAE | 2.00 days |
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb, MMAE in Serum: Time to Maximum Concentration (Tmax) at Cycle 1 Day 1 | ADC | 0.0340 days |
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb, MMAE in Serum: Time to Maximum Concentration (Tmax) at Cycle 1 Day 1 | TAb | 0.0340 days |
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.
Time frame: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
Population: PKAS population with available data were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb, MMAE in Serum: Time to Maximum Concentration (Tmax) at Cycle 1 Day 15 | ADC | 0.0337 days |
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb, MMAE in Serum: Time to Maximum Concentration (Tmax) at Cycle 1 Day 15 | TAb | 0.0337 days |
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb, MMAE in Serum: Time to Maximum Concentration (Tmax) at Cycle 1 Day 15 | MMAE | 1.93 days |
Primary
PK of ADC, TAb, MMAE in Serum: Volume of Distribution at Steady State (Vss)
Vss was derived from the PK blood samples collected.
Time frame: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
Population: PKAS population with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb, MMAE in Serum: Volume of Distribution at Steady State (Vss) | TAb | 4.97 Liters | Standard Deviation 1.27 |
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb, MMAE in Serum: Volume of Distribution at Steady State (Vss) | ADC | 7.13 Liters | Standard Deviation 1.39 |
| Enfortumab Vedotin 1.25 mg/kg | PK of ADC, TAb, MMAE in Serum: Volume of Distribution at Steady State (Vss) | MMAE | 28900 Liters | Standard Deviation 10800 |
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.
Time frame: Cycle 1 Day 1 : pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
Population: PKAS population with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | PK of MMAE in Serum: Area Under Concentration-time Curve From 0 to Day 7 (AUC0-7d) at Cycle 1 Day 1 | 16.9 day*ng/mL | Standard Deviation 9.21 |
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.
Time frame: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
Population: PKAS population with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | PK of MMAE in Serum: Area Under Concentration-time Curve From 0 to Day 7 (AUC0-7d) at Cycle 1 Day 15 | 23.3 day*ng/mL | Standard Deviation 16.4 |
Primary
PK of MMAE in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 15
Cmax was derived from the PK blood samples collected.
Time frame: Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)
Population: PKAS population with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | PK of MMAE in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 15 | 4.49 ng/mL | Standard Deviation 3.58 |
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.
Time frame: Cycle 1 Day 1: pre-dose
Population: PKAS population.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | PK of MMAE in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 1 | 0 ng/mL |
Primary
PK of MMAE in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 15
Ctrough was derived from the PK blood samples collected.
Time frame: Cycle 1 Day 15: pre-dose
Population: PKAS population with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | PK of MMAE in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 15 | 1880 picograms per milliliter (pg/mL) | Standard Deviation 1680 |
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.
Time frame: Cycle 1 Day 1: pre-dose, end of infusion (EOI), 2 hour, 4 hour post-dose (each cycle = 28 days)
Population: PKAS population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | PK of Monomethyl Auristatin E (MMAE) in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 1 | 3.33 nanograms per milliliter (ng/mL) | Standard Deviation 1.74 |
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.
Time frame: From first dose up to progressive disease or death (maximum duration: 9.33 months)
Population: FAS population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | Disease Control Rate (DCR) as Per RECIST V1.1 Per Investigator's Assesment | 82.5 percentage of 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.
Time frame: From first dose up to progressive disease or death (maximum duration: 9.33 months)
Population: FAS population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | Disease Control Rate (DCR) as Per RECIST V1.1 Per IRC | 72.5 percentage of participants |
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.
Time frame: From date of the first CR/PR up to progressive disease or death (maximum duration: 9.33 months)
Population: FAS population with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | Duration of Response (DOR) as Per RECIST V1.1 Per Investigator's Assessment | NA months |
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.
Time frame: From date of the first CR/PR up to progressive disease or death (maximum duration: 9.33 months)
Population: FAS population with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | Duration of Response (DOR) as Per RECIST V1.1 Per IRC | NA months |
Secondary
Number of Participants With Antitherapeutic Antibodies (ATA)
Number of participants with ATA were reported.
Time frame: From first dose until 9.33 months
Population: FAS population with available data were analyzed.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | Number of Participants With Antitherapeutic Antibodies (ATA) | Baseline Negative, Negative post-baseline | 37 Participants |
| Enfortumab Vedotin 1.25 mg/kg | Number of Participants With Antitherapeutic Antibodies (ATA) | Baseline Negative, Positive post-baseline | 0 Participants |
| Enfortumab Vedotin 1.25 mg/kg | Number of Participants With Antitherapeutic Antibodies (ATA) | Baseline Positive, Negative post-baseline | 1 Participants |
| Enfortumab Vedotin 1.25 mg/kg | Number of Participants With Antitherapeutic Antibodies (ATA) | Baseline Positive, Positive post-baseline | 0 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. 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.
Time frame: End of Treatment (Baseline up to 9.33 months)
Population: SAF population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) | ECOG PS= 2 | 1 Participants |
| Enfortumab Vedotin 1.25 mg/kg | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) | ECOG PS= 3 | 1 Participants |
| Enfortumab Vedotin 1.25 mg/kg | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) | ECOG PS= 0 | 2 Participants |
| Enfortumab Vedotin 1.25 mg/kg | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) | ECOG PS= 1 | 8 Participants |
| Enfortumab Vedotin 1.25 mg/kg | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) | ECOG PS= 4 | 0 Participants |
| Enfortumab Vedotin 1.25 mg/kg | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) | ECOG PS= 5 | 0 Participants |
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.
Time frame: Baseline up to 9.33 months
Population: Safety analysis set (SAF) included all participants who were enrolled and received any amount of study drug in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | Number of Participants With Treatment Emergent Adverse Events | 40 Participants |
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.
Time frame: From first dose up to progressive disease or death (maximum duration: 9.33 months)
Population: FAS population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | Objective Response Rate (ORR) as Per Investigator Assessment | 42.5 percentage of participants |
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.
Time frame: From first dose up to death (maximum duration: 9.33 months)
Population: FAS population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | Overall Survival (OS) | NA months |
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.
Time frame: From first dose up to progressive disease or death (maximum duration: 9.33 months)
Population: FAS population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | Progression Free-Survival Per RECIST V1.1 Per Investigator's Assessment | 4.24 months |
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.
Time frame: From first dose up to progressive disease or death (maximum duration: 9.33 months)
Population: FAS population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enfortumab Vedotin 1.25 mg/kg | Progression Free-Survival Per RECIST V1.1 Per IRC | 4.67 months |