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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04879329




Registration number
NCT04879329
Ethics application status
Date submitted
19/04/2021
Date registered
10/05/2021
Date last updated
2/07/2025

Titles & IDs
Public title
A Study of Disitamab Vedotin Alone or With Pembrolizumab in Urothelial Cancer That Expresses HER2
Scientific title
A Phase 2 Multi-Cohort, Open-Label, Multi-Center Clinical Study Evaluating the Efficacy and Safety of Disitamab Vedotin (RC48-ADC) Alone or in Combination With Pembrolizumab in Subjects With Locally-Advanced Unresectable or Metastatic Urothelial Carcinoma That Expresses HER2
Secondary ID [1] 0 0
C5731002
Secondary ID [2] 0 0
RC48G001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Urothelial Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Bladder - transitional cell cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - disitamab vedotin
Treatment: Drugs - pembrolizumab

Experimental: Cohort A - DV monotherapy for HER2-positive tumor types - Disitamab vedotin monotherapy

Experimental: Cohort B - DV monotherapy for HER2-low tumor types - Disitamab vedotin monotherapy

Experimental: Cohort C - Non-randomized combination therapy - Disitamab vedotin + pembrolizumab

Experimental: Cohort C - Randomized combination therapy - Disitamab vedotin + pembrolizumab

Experimental: Cohort C - Randomized monotherapy - Disitamab vedotin monotherapy

Experimental: Cohort D - DV monotherapy (Japan only) - Disitamab vedotin monotherapy

Experimental: Cohort E - DV combination therapy (Japan only) - Disitamab vedotin + pembrolizumab

Experimental: Cohort G - DV monotherapy - Disitamab vedotin


Treatment: Drugs: disitamab vedotin
Given into the vein (IV; intravenous) every 2 weeks.

Treatment: Drugs: pembrolizumab
Given by IV on Day 1 of each 6-week cycle.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Confirmed Objective Response Rate (cORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) by blinded independent central review (BICR) (Cohorts A, B, C, and G)
Timepoint [1] 0 0
Duration of treatment; approximately 2 years
Primary outcome [2] 0 0
Incidence of adverse events (AEs) (Cohorts D and E)
Timepoint [2] 0 0
Approximately 2 years
Primary outcome [3] 0 0
Incidence of dose alterations (Cohorts D and E)
Timepoint [3] 0 0
Approximately 2 years
Primary outcome [4] 0 0
Incidence of laboratory abnormalities (Cohorts D and E)
Timepoint [4] 0 0
Approximately 2 years
Primary outcome [5] 0 0
Incidence of electrocardiogram (ECG) abnormalities (Cohorts D and E)
Timepoint [5] 0 0
Approximately 2 years
Primary outcome [6] 0 0
Change from baseline of left ventricular ejection fraction (LVEF) (Cohorts D and E)
Timepoint [6] 0 0
Approximately 2 years
Primary outcome [7] 0 0
Pharmacokinetic (PK) parameter - Area under the curve (AUC) (Cohorts D and E)
Timepoint [7] 0 0
Through 30-37 days following the last dose of DV; up to approximately 2 years
Primary outcome [8] 0 0
PK parameter - Maximum concentration (Cmax) (Cohorts D and E)
Timepoint [8] 0 0
Through 30-37 days following the last dose of DV; up to approximately 2 years
Primary outcome [9] 0 0
PK parameter - Time to maximum concentration (Tmax) (Cohorts D and E)
Timepoint [9] 0 0
Through 30-37 days following the last dose of DV; up to approximately 2 years
Primary outcome [10] 0 0
PK parameter - Trough concentration (Ctrough) (Cohorts D and E)
Timepoint [10] 0 0
Through 30-37 days following the last dose of DV; up to approximately 2 years
Secondary outcome [1] 0 0
cORR per RECIST v1.1 by investigator assessment (Cohorts A, B, C, and G)
Timepoint [1] 0 0
Duration of treatment; approximately 2 years
Secondary outcome [2] 0 0
Confirmed Duration of Response (DOR) per RECIST v1.1 by BICR (Cohorts A, B, C, and G)
Timepoint [2] 0 0
From start of treatment to completion of response assessment; approximately 2 years
Secondary outcome [3] 0 0
Confirmed DOR per RECIST v1.1 by investigator assessment (Cohorts A, B, C, and G)
Timepoint [3] 0 0
From start of treatment to completion of response assessment; approximately 2 years
Secondary outcome [4] 0 0
Progression-free survival (PFS) per RECIST v1.1 by BICR (Cohorts A, B, C, and G)
Timepoint [4] 0 0
From start of treatment to completion of response assessment; approximately 2 years
Secondary outcome [5] 0 0
PFS per RECIST v1.1 by investigator assessment (Cohorts A, B, C, and G)
Timepoint [5] 0 0
From start of treatment to completion of response assessment; approximately 2 years
Secondary outcome [6] 0 0
Disease control rate (DCR) per RECIST v1.1 by BICR (Cohorts A, B, C, and G)
Timepoint [6] 0 0
From start of treatment to completion of response assessment; approximately 2 years
Secondary outcome [7] 0 0
DCR per RECIST v1.1 by investigator (Cohorts A, B, C, and G)
Timepoint [7] 0 0
From start of treatment to completion of response assessment; approximately 2 years
Secondary outcome [8] 0 0
Overall survival (OS) (Cohorts A, B, C, and G)
Timepoint [8] 0 0
Duration of study; approximately 3 years
Secondary outcome [9] 0 0
Incidence of adverse events (AEs) (Cohorts A, B, C, and G)
Timepoint [9] 0 0
Approximately 2 years
Secondary outcome [10] 0 0
Incidence of dose alterations (Cohorts A, B, C, and G)
Timepoint [10] 0 0
Approximately 2 years
Secondary outcome [11] 0 0
Incidence of laboratory abnormalities (Cohorts A, B, C, and G)
Timepoint [11] 0 0
Approximately 2 years
Secondary outcome [12] 0 0
Incidence of ECG abnormalities (Cohorts A, B, C, and G)
Timepoint [12] 0 0
Approximately 2 years
Secondary outcome [13] 0 0
Change from baseline of LVEF (Cohorts A, B, C, and G)
Timepoint [13] 0 0
Approximately 2 years
Secondary outcome [14] 0 0
PK parameter - AUC (Cohorts A, B, C, and G)
Timepoint [14] 0 0
Through 30-37 days following the last dose of DV; up to approximately 2 years
Secondary outcome [15] 0 0
PK parameter - Cmax (Cohorts A, B, C, and G)
Timepoint [15] 0 0
Through 30-37 days following the last dose of DV; up to approximately 2 years
Secondary outcome [16] 0 0
PK parameter - Tmax (Cohorts A, B, C, and G)
Timepoint [16] 0 0
Through 30-37 days following the last dose of DV; up to approximately 2 years
Secondary outcome [17] 0 0
PK parameter - Ctrough (Cohorts A, B, C, and G)
Timepoint [17] 0 0
Through 30-37 days following the last dose of DV; up to approximately 2 years
Secondary outcome [18] 0 0
PK parameter of pembrolizumab - Cmax (Cohort E)
Timepoint [18] 0 0
Through 30-37 days following the last dose of DV; up to approximately 2 years
Secondary outcome [19] 0 0
Incidence of anti-drug antibodies (ADAs) against disitamab vedotin (All Cohorts)
Timepoint [19] 0 0
Through 30-37 days following the last dose of DV; up to approximately 2 years
Secondary outcome [20] 0 0
Incidence of anti-drug antibodies (ADAs) against pembrolizumab (Cohorts C and E)
Timepoint [20] 0 0
Through 30-37 days following the last dose of DV; up to approximately 2 years
Secondary outcome [21] 0 0
Incidence of neutralizing antibodies (NABs) against disitamab vedotin (All Cohorts)
Timepoint [21] 0 0
Through 30-37 days following the last dose of DV; up to approximately 2 years

Eligibility
Key inclusion criteria
Cohorts A and B

* Histopathologically-confirmed, locally-advanced, unresectable or metastatic urothelial cancer (LA/mUC), including UC originating from the renal pelvis, ureters, bladder, or urethra
* Participants must have received only 1 or 2 lines of prior systemic treatment for LA/mUC, including 1 line of platinum-containing chemotherapy
* At least one measurable lesion by investigator assessment based on RECIST version 1.1.
* HER2-expression status determined by the central laboratory to be IHC 1+, 2+ or 3+, in the provided tumor sample
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

Cohort C

* Histopathologically-confirmed LA/mUC, including UC originating from the renal pelvis, ureters, bladder, or urethra
* No prior systemic therapy for LA/mUC

* Neoadjuvant or adjuvant therapy, including PD-(L)1 inhibitors, is acceptable, if disease recurrence/progression occurred more than 12 months after the last dose of systemic therapy
* At least one measurable lesion by investigator assessment based on RECIST v1.1.
* Participant is eligible to receive cisplatin- or carboplatin- containing chemotherapy per investigator evaluation
* HER2-expression status determined by the central laboratory to be IHC 1+, 2+ or 3+, on the provided tumor tissue sample
* ECOG performance status of 0, 1, or 2

Cohort D

* Histopathologically-confirmed LA/mUC, including UC originating from the renal pelvis, ureters, bladder, or urethra
* Based on a participant's eligibility to receive treatment with standard of care therapies in Japan, participants must have received all of the following lines of therapy for LA/mUC:

* a. One prior line of platinum-containing chemotherapy.
* b. Prior therapy with PD-(L)1 inhibitors as (neo)adjuvant therapy, first-line maintenance therapy or as second line treatment.
* c. Prior enfortumab vedotin therapy.
* At least one measurable lesion by investigator assessment based on RECIST v1.1.
* ECOG performance status of 0 or 1

Cohort E

* Histopathologically-confirmed LA/mUC, including UC originating from the renal pelvis, ureters, bladder, or urethra
* No prior systemic therapy for LA/mUC

* Neoadjuvant or adjuvant therapy, including PD-(L)1 inhibitors, is acceptable, if disease recurrence/progression occurred more than 12 months after the last dose of systemic therapy.
* At least one measurable lesion by investigator assessment based on RECIST v1.1.
* Participant is eligible to receive cisplatin- or carboplatin- containing chemotherapy per investigator evaluation
* HER2-expression status determined by the central laboratory to be IHC 1+, 2+ or 3+, in the provided tumor sample
* ECOG performance status of 0 or 1

Cohort G

* Histopathologically-confirmed, locally-advanced, unresectable or metastatic urothelial cancer (LA/mUC), including UC originating from the renal pelvis, ureters, bladder, or urethra
* Participants must have received only 1 or 2 lines of prior systemic treatment for LA/mUC, including 1 line of therapy containing enfortumab vedotin as monotherapy or in combination with pembrolizumab

* The last administration of enfortumab vedotin must be 90 days from the start of study treatment. Intervening therapies are allowed between the final dose of enfortumab vedotin and the start of disitamab vedotin.
* At least one measurable lesion by investigator assessment based on RECIST version 1.1.
* HER2-expression status determined by the central laboratory to be IHC 1+, 2+ or 3+, in the provided tumor sample
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Cohorts A and B

* Known hypersensitivity to disitamab vedotin or any of their components
* Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study (defined as Cycle 1 Day 1 for Cohorts A and B)
* Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia)
* Prior MMAE-based ADCs (eg, enfortumab vedotin) or HER2-directed therapy
* Major surgery that has not fully recovered within 4 weeks prior to dose administration
* Peripheral sensory or motor neuropathy = Grade 2 at baseline

Cohort C

* Known hypersensitivity to disitamab vedotin, pembrolizumab, or any of their components
* Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study defined as Cycle 1 Day 1 for the single-arm part of Cohort C and as randomization date for the randomized part of Cohort C)
* Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia)
* Prior MMAE-based ADCs (eg, enfortumab vedotin) or HER2-directed therapy
* Major surgery that has not fully recovered within 4 weeks prior to dose administration
* Peripheral sensory or motor neuropathy = Grade 2 at baseline
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug
* Participants who have previously received any 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) are excluded.

Cohort D

* Known hypersensitivity to disitamab vedotin or any of their components
* Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study (defined as Cycle 1 Day 1 for Cohort D)
* Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia)
* Prior HER2-directed therapy
* Any prior history of = Grade 3 non-hematological AEs related to prior therapy
* Major surgery that has not fully recovered within 4 weeks prior to dose administration
* Peripheral sensory or motor neuropathy = Grade 1 at baseline

Cohort E

* Known hypersensitivity to disitamab vedotin, pembrolizumab, or any of their components
* Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study (defined as Cycle 1 Day 1 for Cohort E)
* Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia)
* Any prior history of = Grade 3 non-hematological AEs related to prior therapy
* Prior MMAE-based ADCs (eg, enfortumab vedotin) or HER2-directed therapy
* Major surgery that has not fully recovered within 4 weeks prior to dose administration
* Peripheral sensory or motor neuropathy = Grade 1 at baseline
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug

Cohort G

* Known hypersensitivity to disitamab vedotin or any of their components
* Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study (defined as Cycle 1 Day 1 for Cohort G)
* Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia)
* Prior HER2-directed therapy
* Major surgery that has not fully recovered within 4 weeks prior to dose administration
* Peripheral sensory or motor neuropathy = Grade 2 at baseline

There are additional inclusion and exclusion criteria. The study center will determine if criteria for participation are met.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
GenesisCare - North Shore - St Leonards
Recruitment hospital [2] 0 0
Macquarie University - Sydney
Recruitment hospital [3] 0 0
Mater Cancer Care Centre, Mater Misericordiae Limited - South Brisbane
Recruitment hospital [4] 0 0
Peninsula & South Eastern Haematology and Oncology Group - Frankston
Recruitment hospital [5] 0 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [6] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
2109 - Sydney
Recruitment postcode(s) [3] 0 0
QLD 4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
3199 - Frankston
Recruitment postcode(s) [5] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [6] 0 0
4102 - Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
Oklahoma
Country [14] 0 0
United States of America
State/province [14] 0 0
Tennessee
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Utah
Country [17] 0 0
United States of America
State/province [17] 0 0
Virginia
Country [18] 0 0
United States of America
State/province [18] 0 0
Washington
Country [19] 0 0
United States of America
State/province [19] 0 0
Wisconsin
Country [20] 0 0
Argentina
State/province [20] 0 0
RIO Negro
Country [21] 0 0
Argentina
State/province [21] 0 0
Caba
Country [22] 0 0
Argentina
State/province [22] 0 0
Ciudad autonoma de Buenos Aires
Country [23] 0 0
Argentina
State/province [23] 0 0
Ciudad Autonoma de Buenos Aires
Country [24] 0 0
Argentina
State/province [24] 0 0
Cordoba
Country [25] 0 0
Argentina
State/province [25] 0 0
Viedma
Country [26] 0 0
Belgium
State/province [26] 0 0
Gent
Country [27] 0 0
Belgium
State/province [27] 0 0
Namur
Country [28] 0 0
Canada
State/province [28] 0 0
Alberta
Country [29] 0 0
Canada
State/province [29] 0 0
British Columbia
Country [30] 0 0
Canada
State/province [30] 0 0
Manitoba
Country [31] 0 0
Canada
State/province [31] 0 0
Quebec
Country [32] 0 0
Canada
State/province [32] 0 0
Québec
Country [33] 0 0
Canada
State/province [33] 0 0
Vancouver
Country [34] 0 0
Canada
State/province [34] 0 0
Winnipeg
Country [35] 0 0
Chile
State/province [35] 0 0
Providencia
Country [36] 0 0
Chile
State/province [36] 0 0
La Serena
Country [37] 0 0
Israel
State/province [37] 0 0
Haifa
Country [38] 0 0
Israel
State/province [38] 0 0
Petach Tikva
Country [39] 0 0
Israel
State/province [39] 0 0
Ramat Gan
Country [40] 0 0
Israel
State/province [40] 0 0
Ramat-Gan
Country [41] 0 0
Israel
State/province [41] 0 0
Tel Aviv
Country [42] 0 0
Italy
State/province [42] 0 0
Lombardy
Country [43] 0 0
Italy
State/province [43] 0 0
Pordenone
Country [44] 0 0
Italy
State/province [44] 0 0
Rome
Country [45] 0 0
Italy
State/province [45] 0 0
Toscana
Country [46] 0 0
Italy
State/province [46] 0 0
Milan
Country [47] 0 0
Italy
State/province [47] 0 0
Padova
Country [48] 0 0
Italy
State/province [48] 0 0
Pisa
Country [49] 0 0
Italy
State/province [49] 0 0
Terni
Country [50] 0 0
Japan
State/province [50] 0 0
Chiba
Country [51] 0 0
Japan
State/province [51] 0 0
Hokkaido
Country [52] 0 0
Japan
State/province [52] 0 0
Osaka
Country [53] 0 0
Japan
State/province [53] 0 0
Tokushima
Country [54] 0 0
Japan
State/province [54] 0 0
Tokyo
Country [55] 0 0
Spain
State/province [55] 0 0
Andaluca
Country [56] 0 0
Spain
State/province [56] 0 0
Barcelona
Country [57] 0 0
Spain
State/province [57] 0 0
Madrid
Country [58] 0 0
Spain
State/province [58] 0 0
Sevilla
Country [59] 0 0
United Kingdom
State/province [59] 0 0
Scotland
Country [60] 0 0
United Kingdom
State/province [60] 0 0
Cambridge
Country [61] 0 0
United Kingdom
State/province [61] 0 0
London
Country [62] 0 0
United Kingdom
State/province [62] 0 0
Manchester
Country [63] 0 0
United Kingdom
State/province [63] 0 0
Merseyside

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Seagen, a wholly owned subsidiary of Pfizer
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Merck Sharp & Dohme LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Country 0 0
Phone 0 0
1-800-718-1021
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.