Recruiting NCT04879329

A Study of Disitamab Vedotin Alone or With Pembrolizumab in Urothelial Cancer That Expresses HER2

Phase II Interventional Urothelial Carcinoma

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: disitamab vedotin, pembrolizumab.
Who it may be relevant to: Registry conditions: Urothelial Carcinoma. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Argentina, Australia, Belgium, Canada +7
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official 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

Overview

This study is being done to see if a drug called disitamab vedotin, alone or with pembrolizumab, works to treat HER2 expressing urothelial cancer. It will also test how safe the drug is for participants. Participants will have cancer that has spread in the body near where it started (locally advanced) and cannot be removed (unresectable) or has spread through the body (metastatic). It will also study what side effects happen when participants get the drug. A side effect is anything a drug does to your body besides treating the disease.

Interventions

Drug disitamab vedotin
Given into the vein (IV; intravenous) every 2 weeks.
Drug pembrolizumab
Given by IV on Day 1 of each 6-week cycle.

Primary outcome measures

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) [Time frame: Duration of treatment; approximately 2 years]
Incidence of adverse events (AEs) (Cohorts D and E) [Time frame: Approximately 2 years]
Incidence of dose alterations (Cohorts D and E) [Time frame: Approximately 2 years]
Incidence of laboratory abnormalities (Cohorts D and E) [Time frame: Approximately 2 years]
Incidence of electrocardiogram (ECG) abnormalities (Cohorts D and E) [Time frame: Approximately 2 years]
Change from baseline of left ventricular ejection fraction (LVEF) (Cohorts D and E) [Time frame: Approximately 2 years]
Pharmacokinetic (PK) parameter - Area under the curve (AUC) (Cohorts D and E) [Time frame: Through 30-37 days following the last dose of DV; up to approximately 2 years]
PK parameter - Maximum concentration (Cmax) (Cohorts D and E) [Time frame: Through 30-37 days following the last dose of DV; up to approximately 2 years]
PK parameter - Time to maximum concentration (Tmax) (Cohorts D and E) [Time frame: Through 30-37 days following the last dose of DV; up to approximately 2 years]
PK parameter - Trough concentration (Ctrough) (Cohorts D and E) [Time frame: Through 30-37 days following the last dose of DV; up to approximately 2 years]

Secondary outcome measures (12)

cORR per RECIST v1.1 by investigator assessment (Cohorts A, B, C, and G) [Time frame: Duration of treatment; approximately 2 years]
Confirmed Duration of Response (DOR) per RECIST v1.1 by BICR (Cohorts A, B, C, and G) [Time frame: From start of treatment to completion of response assessment; approximately 2 years]
Confirmed DOR per RECIST v1.1 by investigator assessment (Cohorts A, B, C, and G) [Time frame: From start of treatment to completion of response assessment; approximately 2 years]
Progression-free survival (PFS) per RECIST v1.1 by BICR (Cohorts A, B, C, and G) [Time frame: From start of treatment to completion of response assessment; approximately 2 years]
PFS per RECIST v1.1 by investigator assessment (Cohorts A, B, C, and G) [Time frame: From start of treatment to completion of response assessment; approximately 2 years]
Disease control rate (DCR) per RECIST v1.1 by BICR (Cohorts A, B, C, and G) [Time frame: From start of treatment to completion of response assessment; approximately 2 years]
DCR per RECIST v1.1 by investigator (Cohorts A, B, C, and G) [Time frame: From start of treatment to completion of response assessment; approximately 2 years]
Overall survival (OS) (Cohorts A, B, C, and G) [Time frame: Duration of study; approximately 3 years]
Incidence of adverse events (AEs) (Cohorts A, B, C, and G) [Time frame: Approximately 2 years]
Incidence of dose alterations (Cohorts A, B, C, and G) [Time frame: Approximately 2 years]
Incidence of laboratory abnormalities (Cohorts A, B, C, and G) [Time frame: Approximately 2 years]
Incidence of ECG abnormalities (Cohorts A, B, C, and G) [Time frame: Approximately 2 years]

Eligibility criteria

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

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Sequential
Masking: Open label
Primary purpose: Treatment