| CTRI Number |
CTRI/2025/07/091091 [Registered on: 17/07/2025] Trial Registered Prospectively |
| Last Modified On: |
15/07/2025 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
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Type of Study
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Drug |
| Study Design |
Other |
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Public Title of Study
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A Phase 3, Open label, Randomized and Controlled Study of Disitamab Vedotin with Pembrolizumab Versus platinum containing chemotherapy in participants with Urothelial cancer that Expresses HER2 that has spread through the body or spread near where it started. |
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Scientific Title of Study
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An Open-label, Randomized, Controlled Phase 3 Study of Disitamab Vedotin in Combination with Pembrolizumab Versus Chemotherapy in Subjects with Previously Untreated Locally Advanced or Metastatic Urothelial Carcinoma that Expresses HER2 (IHC 1+ and Greater) |
| Trial Acronym |
NIL |
|
Secondary IDs if Any
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| Secondary ID |
Identifier |
| 2022-501105-12 |
EudraCT |
| C5731001 Protocol Amendment V 3.0 |
Protocol Number |
| NCT05911295 |
ClinicalTrials.gov |
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
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| Name |
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| Designation |
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| Affiliation |
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| Address |
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| Phone |
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| Fax |
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| Email |
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Details of Contact Person
Scientific Query
|
| Name |
Dr Seema Pai |
| Designation |
Sr Director Clinical Site Operations - India Cluster |
| Affiliation |
Pfizer Limited |
| Address |
The Capital, 1802-1901, Plot No. C-70, G Block, Bandra Kurla Complex, Bandra (East) Mumbai
Mumbai
MAHARASHTRA
400051
India |
| Phone |
02266932000 |
| Fax |
|
| Email |
seema.pai@pfizer.com |
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Details of Contact Person
Public Query
|
| Name |
Dr Seema Pai |
| Designation |
Sr Director Clinical Site Operations - India Cluster |
| Affiliation |
Pfizer Limited |
| Address |
The Capital, 1802-1901, Plot No. C-70, G Block, Bandra Kurla Complex, Bandra (East) Mumbai
Mumbai
MAHARASHTRA
400051
India |
| Phone |
02266932000 |
| Fax |
|
| Email |
seema.pai@pfizer.com |
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Source of Monetary or Material Support
|
| Seagen Inc., a wholly owned subsidiary of Pfizer
21823 30th Drive SE
Bothell, WA 98021, USA |
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Primary Sponsor
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| Name |
Seagen Inc., a wholly owned subsidiary of Pfizer |
| Address |
21823 30th Drive SE
Bothell, WA 98021, USA |
| Type of Sponsor |
Pharmaceutical industry-Global |
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Details of Secondary Sponsor
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| Name |
Address |
| Pfizer Limited |
IIThe Capital, 1802/1901, Plot No. C-70, G Block, Bandra Kurla Complex, Bandra (East), Mumbai
ll400051, Maharashtra, India |
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Countries of Recruitment
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Argentina
Australia
Austria
Belgium
Brazil
Canada
Chile
Czech Republic
France
Greece
Hungary
India
Ireland
Israel
Italy
Japan
Mexico
Netherlands
New Zealand
Norway
Peru
Portugal
Singapore
Spain
Sweden
Taiwan
Thailand
Turkey
United Kingdom
United States of America |
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Sites of Study
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| No of Sites = 9 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Chetan Deshmukh |
Deenanath Mangeshkar Hospital & Research Centre |
Ground Floor, Annex Building, Near Mhatre Bridge, Erandwane, Pune, 411004
Pune
MAHARASHTRA |
912049154456
drchetandeshmukh@gmail.com |
| Dr Velavan Kandappan |
Erode Cancer Centre |
1/393, Velavan Nagar,
Perundurai Road,
Thindal,
Erode 638012,
Tamil Nadu
India
Erode
TAMIL NADU |
9842334222
kvels@rediffmail.com |
| Dr Raj Nagarkar |
HCG Manavata Cancer Centre |
Department of Medical Oncology, Behind Shivang Auto, Mumbai Naka, Nashik 422002, Maharashtra, India
Nashik
MAHARASHTRA |
9823061929
drraj@manavatacancercentre.com |
| Dr Kaushalkumar Patel |
Nirmal Hospital Pvt Ltd |
Department of Clinical Research, Ring Road, Surat,
Gujarat 395002, India
Surat
GUJARAT |
9377113143
drkaushalbpatel@gmail.com |
| Dr Sandeep Jasuja |
R K Birla Cancer Centre, SMS Hospital |
JLN Marg,
Jaipur,
Rajasthan - 302004,
India
Jaipur
RAJASTHAN |
9660121475
sandeepjasuja@gmail.com |
| Dr Vineet Talwar |
Rajiv Gandhi Cancer Institute and Research Centre |
Department of Medical Oncology, Institutional Area, Sector 5,
Rohini, New Delhi - 110085, India
North West
DELHI |
9810241512
drvineettalwar@yahoo.com |
| Dr Tushar Patil |
Sahyadri Super Speciality Hospital |
First Floor, OPD 111, Deccan, 30-C Erandwane, Karve Road,
Pune - 411004, Maharashtra, India
Pune
MAHARASHTRA |
9552522556
tussipats@hotmail.com |
| Dr Satheesh Tungappa |
Spandana Oncology Centre |
Clinical Research Department, 919, New No. 68,
28th Main Road,
9th Block Jayanagar,
Bengaluru - 560069
Bangalore
KARNATAKA |
9242698750
drsatheeshct@gmail.com |
| Dr Amit Joshi |
Tata Memorial Hospital |
Dr Ernest Borges Marg,
Parel,
Mumbai 400012,
Maharashtra,
India
Mumbai
MAHARASHTRA |
9769331525
dramitjoshi74@gmail.com |
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Details of Ethics Committee
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| No of Ethics Committees= 9 |
| Name of Committee |
Approval Status |
| Ethics Committee, SMS Medical College and Attached Hospitals |
Approved |
| IEC for Spandana Oncology Centre, Spandana Oncology Centre |
Approved |
| Institutional Ethics Committee - I, Tata Memorial Hospital |
Submittted/Under Review |
| Institutional Ethics Committee, Deenanath Mangeshkar Hospital and Research Centre |
Approved |
| Institutional Ethics Committee, Erode Cancer Centre Pvt Ltd |
Approved |
| Institutional Ethics Committee, HCG Manavata Cancer Centre |
Submittted/Under Review |
| Institutional Review Board, Rajiv Gandhi Cancer Institute and Research Centre |
Approved |
| Nirmal Hospital Ethics Committee |
Approved |
| Sahyadri Hospital Pvtr Ltd Ethics Committee, Sahyadri Clinical Research and Development Centre |
Approved |
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Regulatory Clearance Status from DCGI
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Health Condition / Problems Studied
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| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: D494||Neoplasm of unspecified behavior of bladder, |
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Intervention / Comparator Agent
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| Type |
Name |
Details |
| Comparator Agent |
Carboplatin |
Carboplatin AUC 4.5 or 5 administered as an IV infusion every 21 days. |
| Comparator Agent |
Cisplatin |
Cisplatin 70mg per m2 administered as an IV infusion every 21 days. |
| Intervention |
Disitamab Vedotin |
Disitamab Vedotin 45mg per vial administered as an IV infusion once every 2 weeks. |
| Comparator Agent |
Gemcitabine |
Gemcitabine 1000mg per m2 administered as an IV infusion every 21 days. |
| Intervention |
Pembrolizumab |
Pembrolizumab 400mg administered as an IV infusion every once 6 weeks. |
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Inclusion Criteria
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| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
1. Histopathological confirmation of locally advanced unresectable or metastatic urothelial carcinoma (LA/mUC), including UC originating from the renal pelvis, ureters, bladder, or urethra.
2. Measurable disease by investigator assessment per RECIST v1.1.
3. Participant must not have received prior systemic therapy for LA/mUC. Exception will be made for neoadjuvant or adjuvant therapy, if disease recurrence/progression occurred more than 12 months after the last dose of therapy.
4. Eligible to receive cisplatin- or carboplatin-containing chemotherapy.
5. Able to provide archived formalin-fixed paraffin-embedded tumor tissue blocks from a muscle-invasive or metastatic UC lesion or biopsy of metastatic UC prior to treatment initiation. If archival tissue is not available a newly obtained baseline biopsy of an accessible tumor lesion is required within 28 days of cycle 1 day 1.
6. HER2 expression of 1+ or greater on immunohistochemistry (IHC).
7. Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1, or 2 within 7 days prior to randomization. |
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| ExclusionCriteria |
| Details |
1. Known hypersensitivity to disitamab vedotin, cisplatin, carboplatin, gemcitabine, or pembrolizumab or any of their components.
2. History of severe/life threatening immune-related adverse event (irAE) with PD-(L)1 inhibitors are excluded.
Central nervous system (CNS) and/or leptomeningeal metastasis. Participants with treated
3.CNS metastases are permitted if all of the following are met.
- CNS metastases have been clinically stable for at least 4 weeks and baseline scans show no evidence of new or worsening CNS metastasis.
- Participant is on a stable dose of less than equal to 10 mg/day of prednisone or equivalent for at least 2 weeks.
3. History of or active autoimmune disease that has required systemic treatment in the past 2 years.
4. Prior treatment with an agent directed to another stimulatory or co-inhibitory T cell receptor (including but not limited to CD137 agonists, CAR-T cell therapy, CTLA-4 inhibitors, or OX-40 agonists).
5. Prior solid organ or bone marrow transplantation.
6. Pleural effusion or ascites with symptoms or requiring symptomatic treatment.
7. Estimated life expectancy less than 12 week
8. Prior treatment with an MMAE agent or anti-HER2 therapy |
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Method of Generating Random Sequence
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Other |
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Method of Concealment
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Other |
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Blinding/Masking
|
Open Label |
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Primary Outcome
|
| Outcome |
TimePoints |
1. To compare the efficacy of disitamab vedotin in combination with pembrolizumab to chemotherapy as firstline treatment in participants with advanced UC that expresses HER2.
2. Overall survival (OS) |
1. Approximately 3 years
2. Approximately 5 years |
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Secondary Outcome
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| Outcome |
TimePoints |
| Objective response rate (ORR) per RECIST v1.1 by BICR |
Approximately 3 years |
| ORR per RECIST v1.1 by investigator assessment |
Approximately 3 years |
| Duration of Response (DOR) per RECIST v1.1 by BICR |
Approximately 3 years |
| DOR per RECIST v1.1 by investigator assessment |
Approximately 3 years |
| Control Rate (DCR) per RECIST v1.1 by BICR |
Approximately 3 years |
| DCR per RECIST v1.1 by investigator assessment |
Approximately 3 years |
| PFS per RECIST v1.1 by investigator assessment |
Approximately 3 years |
| Number of participants with adverse events (AEs) |
Through 30 days after the last study treatment; approximately 2 years |
| Change from baseline of left ventricular ejection fraction (LVEF) |
Through 2 years after last study treatment; approximately 4 years |
| Change from baseline to Week 16 in European Organization for Research and Treatment of Cancer core Quality of Life questionnaire (EORTC QLQ-C30) Global Health Status (GHS)/QoL Score |
Approximately 2 years |
| Time to Deterioration in EORTC QLQ-C30 GHS/QoL Score |
Approximately 2 years |
| Time to pain progression |
Approximately 2 years |
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Target Sample Size
|
Total Sample Size="400"
Sample Size from India="40"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
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Phase of Trial
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N/A |
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Date of First Enrollment (India)
|
15/09/2025 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
01/10/2023 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
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Estimated Duration of Trial
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Years="5"
Months="0"
Days="0" |
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Recruitment Status of Trial (Global)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
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Publication Details
|
N/A |
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Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
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Brief Summary
|
This study will enroll participants with urothelial cancer (UC). UC can include cancer of the bladder, kidney, or the tubes that carry pee through the body (ureter, urethra). This study will try to find out if the drugs disitamab vedotin with pembrolizumab works better than platinum-containing chemotherapy to treat patients with UC. Participants in this study will have cancer that has spread through the body (metastatic) or spread near where it started (locally advanced). In this study, there are 2 different groups. Participants will be assigned to a group randomly. Participants in the disitamab vedotin arm will get the study drug disitamab vedotin once every two weeks and pembrolizumab once every 6 weeks. Participants in the standard of care arm will get gemcitabine once a week for 2 weeks with either cisplatin or carboplatin once every 3 weeks. |