CTRI/2025/05/086631 [Registered on: 09/05/2025] Trial Registered Prospectively
Last Modified On:
31/03/2026
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Biological
Study Design
Single Arm Study
Public Title of Study
This study is being conducted at multiple hospitals in India to check the safety of a medicine called Enfortumab Vedotin in adults who have Urothelial (bladder) cancer that have spread and have already been treated before. The study is in Phase 4 and all participants will receive the medicine
Scientific Title of Study
A Multicenter, Phase 4, Open label, Single-arm, Safety Study of Enfortumab Vedotin in Adult Indian Participants with Previously Treated Locally Advanced or Metastatic Urothelial Cancer
Trial Acronym
NA
Secondary IDs if Any
Secondary ID
Identifier
7465-CL-4001 Protocol Version Amendment 1 dated 06/Dec/2024
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Amit Joshi
Designation
Principal Investigator
Affiliation
Tata Memorial Centre Tata Memorial Hospital
Address
Department of Medical Oncology, Homi Babha Building, Dr Ernest Borges Road Tata Memorial Hospital Parel
Mumbai MAHARASHTRA 400012 India
Phone
9769331525
Fax
Email
dramitjoshi74@gmail.com
Details of Contact Person Scientific Query
Name
Sudhir Madduri Karanam
Designation
Development Scientist
Affiliation
Astellas Pharma Canada Inc
Address
Department Medical Monitoring, 675 Cochrane Drive #650 West Tower Markham
L3R0B8 Other
Phone
6472708010
Fax
Email
Sudhir.Karanam@astellas.com
Details of Contact Person Public Query
Name
Amit Matere
Designation
Project Manager
Affiliation
ICON Clinical Research India Pvt Ltd
Address
Department Clinical Operations, 2nd floor, Prestige Blue Chip Software Park No. 09 Hosur Main Road, Block 2, Opposite Christ College
Bangalore KARNATAKA 560029 India
Phone
9970 500 755
Fax
Email
Amit.Matere@iconplc.com
Source of Monetary or Material Support
Astellas Pharma Global Development Inc., located at 2375, Waterview Drive in Northbrook, Illinois 60062 (USA)
Primary Sponsor
Name
Astellas Pharma Global Development Inc.
Address
Northbrook, IL 60062, US
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
KlinEra Global Services
801, Neelkanth Corporate Park, Opp. Vidyavihar Station Vidyavihar (West)
Vidyavihar-400086, Maharashtra, India.
Amrita Institute of Medical Sciences and Research Center, kochi
Amrita Enterprises Pvt Ltd. Amrita Institute of Medical Sciences. AIMS Ponekkara P O. Kochi – 682041. India Ernakulam KERALA
91-9959353950
nikhilkh@aims.amrita.edu
Dr Bivas Biswas
Apollo Multispeciality Hospitals Limited
58, Canal Circular Road, Kolkata 700 054, India
Kolkata WEST BENGAL
91-9830922005
bivasbiswas@gmail.com
Dr Ashish Singh
Christian Medical College & Hospital (CMCH) Vellore
Department of Medical Oncology, IDA Scudder Road, Vellore 632004
Vellore TAMIL NADU
91-94456 59460
ashishsingh@cmcvellore.ac.in
Dr Chirag Desai
Hemato Oncology Clinic Pvt. Ltd.
Department of Medical Oncology, B/S Occura Eye Hospital & Pandit Dindayal Upadhyay Auditorium, Rajpath Club Road, Off SG Highway, Ahmedabad 380054 Ahmadabad GUJARAT
91-9824047561
chiragdesai.oncology@gmail.com
Dr Ankit Jain
Indraprastha Apollo Hospitals New Delhi
Sarita Vihar, Delhi Mathura Road, 110076 New Delhi DELHI
91-7428106406
drankit_j@apollohospitals.com
Dr Anuj Gupta
Mahamana Pandit Madan Mohan Malaviya Cancer Centre
Department of Medical Oncology, Sundar Bagiya,Near Nariya Gate, Banaras Hindu University Campus, Sunderpur, Varanasi 221005
Varanasi UTTAR PRADESH
91-95882 29594
dr.anuj.gupta24@gmail.com
Dr Ashish Joshi
MOC Cancer Care & Research Centre Mumbai
Department of Medical Oncology, 1st Floor, SS House, Nehru Road, Navpada, Vileparle, Mumbai 400057 Mumbai MAHARASHTRA
91-9833662891
ashjoshi44@mocindia.co.in
Dr Anand Pathak
National Cancer Institute Nagpur
Department of Medical Oncology, Outer Ring Road, Jamtha, Nagpur 441108 Nagpur MAHARASHTRA
91-9823038498
abpathak21@gmail.com
Dr Anshul Agarwal
Nirmal Hospital Pvt Ltd.
Department of Medical Oncology, Centre Point, Ring Road, Near Kadiwala School, Surat 395002
Surat GUJARAT
91-74056 98000
anshul.onco@gmail.com
Dr Sandeep Kumar Jasuja
R.K Birla Cancer Centre, SMS Medical College and Attached Hospital
Department of Medical Oncology & BMT, JLN Marg, jaipur 302004
Jaipur RAJASTHAN
91-96601 21475
sandeepjasuja@gmail.com
Prof Ghanashyam Biswas
Sparsh Hospitals and Critical Care Private Limited
Department of Medical Oncology, A-407, Saheed Nagar, Bhubaneswar, Odisha, 751007 Khordha ORISSA
91-9937500878
drgbiswas@gmail.com
Dr Rajesh Singh
State Cancer Institute - Indira Gandhi Institute of Medical Sciences
Sheikhpura, Patna Sheikhpura BIHAR
91-9939088899
drrajeshrccigimstrial@gmail.com
Dr Ankit patel
Sunshine Global Hospital, Surat
Dumas Rd, beside Big Bazar, Piplod, Surat, Gujarat 395007, India Surat GUJARAT
91-9825404202
drankitoncologist@gmail.com
Dr Amit Joshi
Tata Memorial Centre, Tata Memorial Hospital
Department of Medical Oncology, Homi Babha Building, Dr Ernest Borges Road, Tata Memorial Hospital, Parel, Mumbai 400012
Mumbai MAHARASHTRA
91-97693 31525
dramitjoshi74@gmail.com
Dr Kaushal Kalra
Vardhman Mahavir Medical College and Safdarjung Hospital (VMMC-SJH) New Delhi
Ansari Nagar East, near to AIIMS Metro Station, New Delhi, Delhi 110029, India New Delhi DELHI
Institutional Review Board Christian Medical College
Approved
lnstitutional Ethics Committee Amrita lnstitute of Medical Sciences
Approved
Mumbai Oncocare Centre Institutional Ethic Committee
Approved
National Cancer Institute Ethics Committee
Approved
Nirmal Hospital Ethics Committee
Approved
TMH, Institional Ethics Committee II
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C689||Malignant neoplasm of urinary organ, unspecified,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Enfortumab Vedotin
Solution for injection 1.25 mg/kg (maximum dose 125 mg)
Intervention Label: Enfortumab vedotin
Intervention Name: Enfortumabvedotin
Type: Drug
Pharmaceutical Dose Form: Lyophilized powder for reconstitution
Unit Dose: Strength(s) 30 mg Dosage Level(s): 1.25 mg/kg(maximum dose 125 mg) On days 1, 8, and 15 of a 28-day cycle Route ofAdministration: Intravenous infusion Use: Experimental
IMP and NIMP/AxMPIMP: Intended Sourcing Provided centrally by sponsor
Packaging and Labeling: Supplied as lyophilized powder in single-dose vial for reconstitution
AxMP: auxiliary medicinal product; IMP: investigational medicinal product;NIMP: noninvestigational medicinal product.
Comparator Agent
Not applicable
Not applicable
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
Age
1. Participant is more than or equal to 18 years of age at the time of signing the ICF.
Type of Participant and Disease Characteristics
2. Participant has histologically or cytologically confirmed urothelial carcinoma (i.e., cancer of the bladder, renal pelvis, ureter or urethra). Participants with urothelial carcinoma (transitional cell) with squamous differentiation or mixed cell types are eligible.
3. Participant must have experienced radiographic progression or relapse during or after a CPI (anti-PD-1 or anti-PD-L1) for LA or metastatic disease. Participants who discontinued CPI treatment due to toxicity are eligible provided that they have evidence of disease progression following discontinuation. The CPI need not be the most recent therapy. Participants for whom the most recent therapy has been a non-CPI based
regimen are eligible if they have progressed/relapsed during or after their most recent therapy. LA disease must not be amenable to resection with curative intent per the treating physician.
4. Participant must have received a platinum-containing regimen (cisplatin or carboplatin)
in the metastatic/LA, neoadjuvant or adjuvant setting. If platinum was administered in the adjuvant/neoadjuvant setting, the participant must have progressed within 12 months of completion.
5. Participant must have measurable metastatic or LA disease at baseline according to RECIST version 1.1.
6. Participant has ECOG performance status of 0 or 1.
7. Participant has the following baseline laboratory data -
- ANC more than or equal to 1500/cubic mm
- Platelet count more than or equal to 100000000000/L
- Hemoglobin more than or equal to 9 g/dL
- CrCl more than or equal to 30 mL/min as estimated per institutional standards or as measured by 24-hour urine collection (GFR can also be used instead of CrCl)
- ALT and AST less than or equal to 2.5 × ULN or less than or equal to 3 × ULN for participants with liver metastases.
8. Female participant:
• Not pregnant (see [Section 10.2]) and at least 1 of the following conditions apply:
a. Not a WOCBP (see [Section 10.2])
b. WOCBP who has a negative urine or serum pregnancy test at screening or within 7 days prior to day 1 and agrees to follow the contraceptive guidance (see [Section 10.2]) from the time of informed consent through at least 6 months after
final study intervention administration.
• Must not be breastfeeding or lactating starting at screening and throughout the investigational period and for approximately 6 months after final study intervention administration.
• Must not donate ova starting at first administration of study intervention and throughout the investigational period and for 6 months after final study intervention administration.
9. Male participant:
• Must agree to use contraception (see [Section 10.2]) with female partner(s) of childbearing potential (including breastfeeding partner) throughout the treatment period and for 6 months after final study intervention administration.
• Must agree to remain abstinent or use a condom with pregnant partner(s) for the duration of the pregnancy throughout the investigational period and for 6 months after final study intervention administration.
• Must not donate sperm during the treatment period and for 6 months after final study intervention administration.
Informed Consent
10. Participant has provided informed consent as described in [Section 10.1.3] which includes compliance with the requirements and restrictions listed in the ICF and protocol.
Other Inclusion Criteria
11. Participant agrees not to participate in another interventional study while receiving study
intervention in the present study.
ExclusionCriteria
Details
Medical Conditions
1. Participant has preexisting sensory or motor neuropathy grade more than or equal to 2.
2. Participant has active CNS metastases. Participant with treated CNS metastases is
permitted on study if all the following are true:
- CNS metastases have been clinically stable for at least 6 weeks prior to screening
- If requiring steroid treatment for CNS metastases, the participant is on a stable dose
less than or equal to 20 mg/day of prednisone or equivalent for at least 2 weeks
- Baseline scans show no evidence of new or enlarged brain metastasis
- Participant does not have leptomeningeal disease
3. 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 less than or equal to grade 2 immunotherapy-related hypothyroidism or
panhypopituitarism may be enrolled when well-maintained/controlled on a stable dose of HRT (if indicated).
- Participant with ongoing more than or equal to grade 3 immunotherapy-related hypothyroidism or
panhypopituitarism are excluded.
Participant with ongoing immunotherapy-related colitis, uveitis, myocarditis or pneumonitis, or participant with other immunotherapy-related AEs requiring high doses of steroids (more than 20 mg/day of prednisone or equivalent) are excluded.
4. Participant has history of another malignancy within 3 years before the first dose of
study intervention or any evidence of residual disease from a previously diagnosed malignancy.
- Participant 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.
5. Participant with a positive hepatitis B surface antigen and/or anti-hepatitis B core antibody and a negative polymerase chain reaction assay at baseline should receive appropriate antiviral prophylaxis or regular surveillance monitoring as per local or institutional guidelines.
6. Participant has active hepatitis C infection or known human immunodeficiency virus infection. Participant who has been treated for hepatitis C infection is permitted if they have documented sustained virologic response of more than or equal to 12 weeks.
7. 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 to IV within 6 months prior to the first dose of study intervention administration.
8. Participant has known active keratitis or corneal ulcerations. Participant with superficial
punctate keratitis is allowed if the disorder is being adequately treated in the opinion of the investigator.
9. Participant has other underlying medical condition that, in the opinion of the
investigator, would impair the ability of the participant to receive or tolerate the planned
treatment and follow-up.
10. Participant has history of uncontrolled diabetes mellitus within 3 months of the first dose of study intervention. Uncontrolled diabetes is defined as HbA1c more than or equal to 8% or HbA1c between 7% and less than 8% with associated diabetes symptoms (polyuria or polydipsia) that
are not otherwise explained.
Prior/Concomitant Therapy
11. Participant has prior treatment with enfortumab vedotin or other MMAE-based ADCs.
12. Participant is currently receiving systemic antimicrobial treatment for viral, bacterial, or
fungal infection at the time of first dose of enfortumab vedotin. Routine antimicrobial
prophylaxis is permitted.
13. Participant has radiotherapy or major surgery within 4 weeks prior to first dose study
intervention administration.
14. Participant has had chemotherapy, biologics, investigational agents, and/or antitumor
treatment with immunotherapy that is not completed 2 weeks prior to first dose of study intervention administration.
Other Exclusion Criteria
15. Participant has any condition, which, in the investigator’s opinion, makes the participant
unsuitable for study participation.
16. Participant has a known or suspected 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.
Method of Generating Random Sequence
Other
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To evaluate the safety and tolerability of EV in adult Indian participants with LA or mUC
Every 8 weeks
Secondary Outcome
Outcome
TimePoints
To evaluate the anti-tumor activity of EV as determined by investigator assessment
Every 8 weeks
Target Sample Size
Total Sample Size="100" Sample Size from India="100" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
Title of Study:
A Multicenter, Phase 4, Open-label, Single-arm, Safety Study of Enfortumab Vedotin in Adult Indian Participants with Previously Treated Locally Advanced or Metastatic Urothelial Cancer
Short Title of Study:
A Safety Study of Enfortumab Vedotin in Indian Adults with Urothelial Cancer
Regulatory Agency Identifier Number(s):
Not applicable.
Planned Total Number of Study Sites and Location(s):
Approximately 10 study sites (geographically diverse) in India.
Note: The number of study sites may be adjusted based on participant enrollment.
Rationale:
The primary objective of this study is to assess the safety and tolerability of enfortumab vedotin monotherapy in Indian participants with LA or mUC. The study will also evaluate antitumor activity of enfortumab vedotin in Indian participants. No differences are anticipated in safety, tolerability and efficacy of enfortumab vedotin based on ethnicity from the phase 1, 2, and 3 studies conducted to date. This protocol is part of the post-marketing commitment to the Indian Health Authority after the approval of enfortumab vedotin based on Study 7465-CL-0301 (NCT03474107).
Adult male and female Indian participants with previously treated LA or mUC.
Number of Participants:
One hundred participants will be enrolled.
Study Design Overview:
This is a multicenter, phase 4, open-label, single-arm, safety study of enfortumab vedotin in adult Indian participants with LA or mUC who have received a platinum-containing chemotherapy and have experienced disease progression or relapse during or following treatment with an immune CPI. The study will be conducted at approximately 10 sites (geographically diverse) in India and will enroll 100 participants. The number of study sites may be adjusted based on participant enrollment.
The single-arm study will consist of 3 periods:
• Screening/Baseline period: for a maximum of 28 days prior to the first dose of study intervention defined as cycle 1 day 1.
• Treatment period: beginning at cycle 1 and subsequent cycles until participant discontinues study intervention.
• Follow-up period: beginning after participant discontinues study intervention.
Screening/Baseline Period
After informed consent has been obtained, participants will be evaluated for eligibility by review of medical history, physical examination, weight, vital signs (pulse, temperature and blood pressure),
eye examination, ECOG performance status, imaging assessments (i.e., brain scan and bone scan), blood sample collection and ECG. AEs will be collected during this period. Screening assessments
may be repeated within the 28-day screening period. Participants may only be rescreened once.
Treatment Period
All participants will receive enfortumab vedotin on days 1, 8 and 15 of each 28-day cycle. Participants will continue to receive study intervention until any discontinuation criteria are met, upon study termination or study completion, whichever occurs first. An EOT visit will be performed within 7 days after the last dose of enfortumab vedotin or the decision to discontinue treatment, or prior to initiation of another anticancer therapy, whichever occurs earlier.
Follow-up Periods
30-day Safety Follow-up: Following discontinuation from study intervention or until initiation of a new anticancer treatment, participants will have a 30-day safety follow-up visit 30 days (+ 7 days) after their last dose of study intervention for safety assessments. Post-treatment Follow-up: Participants who discontinue study intervention for reasons other than objective disease progression by RECIST version 1.1 will continue to have response assessments every 8 weeks (± 1 week) following the previous visit thereafter. After 1 year from cycle 1 day 1, the frequency of response assessments will be reduced to every 12 weeks (± 1 week). The tumor assessments will continue until the participant has radiological disease progression per RECIST version 1.1 as determined by investigator assessment, initiates a new anticancer therapy, death, lost to follow-up, study closure, or withdrawal of consent, whichever comes first. The end of the study is defined as the last visit or assessment shown in schedule of assessments for the last participant in the study.
A participant is considered to have completed the study if the participant has completed all periods of the study including the last assessment shown in the schedule of assessments.
Study Intervention Groups and Duration:
Intervention Label
Enfortumab vedotin
Intervention Name
Enfortumab vedotin
Type
Drug
Pharmaceutical Dose Form
Solution for injection
Unit Dose Strength(s)
1.25 mg/kg (maximum dose 125 mg)
Dosage Level(s)
On days 1, 8, and 15 of a 28-day cycle
Route of Administration
Intravenous infusion
Use
Experimental
IMP and NIMP/AxMP
IMP
Intended Sourcing1
Provided centrally by sponsor
Packaging and Labeling
Supplied as lyophilized powder in single-dose vial for reconstitution
1. Planned sourcing may be subject to change based on product availability The anticipated duration of the study for each participant, including screening and follow-up, is approximately 14 months.