The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.

Clinical Trial Details

Geo Regions

Category

Genitourinary Cancer

Disitamab vedotin

Disitamab vedotin is an investigational compound. Its safety and efficacy have not been established.

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
Phase 2
NCT04879329

Active enrolling

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Locations

United States, Argentina, Australia, Belgium, Canada, Chile, Israel, Japan, Spain, United Kingdom

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Study design

Participant Group/Arm

EXPERIMENTAL: Cohort A - DV monotherapy for HER2-positive tumor types

Disitamab vedotin monotherapy

Intervention/Treatment

DRUG: disitamab vedotin

Given into the vein (IV; intravenous) every 2 weeks.

Participant Group/Arm

EXPERIMENTAL: Cohort B - DV monotherapy for HER2-low tumor types

Disitamab vedotin monotherapy

Intervention/Treatment

DRUG: disitamab vedotin

Given into the vein (IV; intravenous) every 2 weeks.

Participant Group/Arm

EXPERIMENTAL: Cohort C - Non-randomized combination therapy

Disitamab vedotin + pembrolizumab

Intervention/Treatment

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.

Participant Group/Arm

EXPERIMENTAL: Cohort C - Randomized combination therapy

Disitamab vedotin + pembrolizumab

Intervention/Treatment

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.

Participant Group/Arm

EXPERIMENTAL: Cohort C - Randomized monotherapy

Disitamab vedotin monotherapy

Intervention/Treatment

DRUG: disitamab vedotin

Given into the vein (IV; intravenous) every 2 weeks.

Participant Group/Arm

EXPERIMENTAL: Cohort D - DV monotherapy (Japan only)

Disitamab vedotin monotherapy

Intervention/Treatment

DRUG: disitamab vedotin

Given into the vein (IV; intravenous) every 2 weeks.

Participant Group/Arm

EXPERIMENTAL: Cohort E - DV combination therapy (Japan only)

Disitamab vedotin + pembrolizumab

Intervention/Treatment

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.

Study design table for Clinical Trial

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

Key dates

Study start date
  • May 2022
Estimated primary completion date
  • May 2028

Key endpoints

Primary Outcome Measures
Outcome Measure

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, and C)

Measure Description

The proportion of participants with confirmed complete response (CR) or partial response (PR) according to RECIST v1.1

Time Frame

Duration of treatment; approximately 2 years

Outcome Measure

Incidence of adverse events (AEs) (Cohorts D and E)

Measure Description

Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.

Time Frame

Approximately 2 years

Outcome Measure

Incidence of dose alterations (Cohorts D and E)

Measure Description

Time Frame

Approximately 2 years

Outcome Measure

Incidence of laboratory abnormalities (Cohorts D and E)

Measure Description

To be summarized using descriptive statistics.

Time Frame

Approximately 2 years

Outcome Measure

Incidence of electrocardiogram (ECG) abnormalities (Cohorts D and E)

Measure Description

Time Frame

Approximately 2 years

Outcome Measure

Change from baseline of left ventricular ejection fraction (LVEF) (Cohorts D and E)

Measure Description

Time Frame

Approximately 2 years

Outcome Measure

Pharmacokinetic (PK) parameter - Area under the curve (AUC) (Cohorts D and E)

Measure Description

To be summarized using descriptive statistics.

Time Frame

Through 30-37 days following the last dose of DV; up to approximately 2 years

Outcome Measure

PK parameter - Maximum concentration (Cmax) (Cohorts D and E)

Measure Description

To be summarized using descriptive statistics.

Time Frame

Through 30-37 days following the last dose of DV; up to approximately 2 years

Outcome Measure

PK parameter - Time to maximum concentration (Tmax) (Cohorts D and E)

Measure Description

To be summarized using descriptive statistics.

Time Frame

Through 30-37 days following the last dose of DV; up to approximately 2 years

Outcome Measure

PK parameter - Trough concentration (Ctrough) (Cohorts D and E)

Measure Description

To be summarized using descriptive statistics.

Time Frame

Through 30-37 days following the last dose of DV; up to approximately 2 years

Primary Outcome Measures table for Clinical Trial
Secondary Outcome Measures:
Outcome Measure

cORR per RECIST v1.1 by investigator assessment (Cohorts A, B, and C)

Measure Description

The proportion of participants with confirmed CR or PR according to RECIST v1.1

Time Frame

Duration of treatment; approximately 2 years

Outcome Measure

Confirmed Duration of Response (DOR) per RECIST v1.1 by BICR (Cohorts A, B, and C)

Measure Description

The time from first documentation of objective tumor response (confirmed CR or PR) to the first documentation of tumor progression per RECIST v1.1 or death due to any cause.

Time Frame

From start of treatment to completion of response assessment; approximately 2 years

Outcome Measure

Confirmed DOR per RECIST v1.1 by investigator assessment (Cohorts A, B, and C)

Measure Description

The time from first documentation of objective tumor response (confirmed CR or PR) to the first documentation of tumor progression per RECIST v1.1 or death due to any cause.

Time Frame

From start of treatment to completion of response assessment; approximately 2 years

Outcome Measure

Progression-free survival (PFS) per RECIST v1.1 by BICR (Cohorts A, B, and C)

Measure Description

The time from the start of study treatment or randomization (if applicable) to the first documentation of disease progression per RECIST v1.1 or death due to any cause.

Time Frame

From start of treatment to completion of response assessment; approximately 2 years

Outcome Measure

PFS per RECIST v1.1 by investigator assessment (Cohorts A, B, and C)

Measure Description

The time from the start of study treatment or randomization (if applicable) to the first documentation of disease progression per RECIST v1.1 or death due to any cause.

Time Frame

From start of treatment to completion of response assessment; approximately 2 years

Outcome Measure

Disease control rate (DCR) per RECIST v1.1 by BICR (Cohorts A, B, and C)

Measure Description

The proportion of participants who have achieved objective response (confirmed CR or PR as per RECIST v1.1 criteria) or stable disease (SD) lasting at least 5 weeks.

Time Frame

From start of treatment to completion of response assessment; approximately 2 years

Outcome Measure

DCR per RECIST v1.1 by investigator (Cohorts A, B, and C)

Measure Description

The proportion of participants who have achieved objective response (confirmed CR or PR as per RECIST v 1.1 criteria) or SD lasting at least 5 weeks.

Time Frame

From start of treatment to completion of response assessment; approximately 2 years

Outcome Measure

Overall survival (OS) (Cohorts A, B, and C)

Measure Description

The time from start of study treatment or randomization (if applicable) to the date of death due to any cause.

Time Frame

Duration of study; approximately 3 years

Outcome Measure

Incidence of adverse events (AEs) (Cohorts A, B, and C)

Measure Description

Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.

Time Frame

Approximately 2 years

Outcome Measure

Incidence of dose alterations (Cohorts A, B, and C)

Measure Description

To be summarized using descriptive statistics.

Time Frame

Approximately 2 years

Outcome Measure

Incidence of laboratory abnormalities (Cohorts A, B, and C)

Measure Description

To be summarized using descriptive statistics.

Time Frame

Approximately 2 years

Outcome Measure

Incidence of ECG abnormalities (Cohorts A, B, and C)

Measure Description

Time Frame

Approximately 2 years

Outcome Measure

Change from baseline of LVEF (Cohorts A, B, and C)

Measure Description

Time Frame

Approximately 2 years

Outcome Measure

PK parameter - AUC (Cohorts A, B, and C)

Measure Description

To be summarized using descriptive statistics.

Time Frame

Through 30-37 days following the last dose of DV; up to approximately 2 years

Outcome Measure

PK parameter - Cmax (Cohorts A, B, and C)

Measure Description

To be summarized using descriptive statistics.

Time Frame

Through 30-37 days following the last dose of DV; up to approximately 2 years

Outcome Measure

PK parameter - Tmax (Cohorts A, B, and C)

Measure Description

To be summarized using descriptive statistics.

Time Frame

Through 30-37 days following the last dose of DV; up to approximately 2 years

Outcome Measure

PK parameter - Ctrough (Cohorts A, B, and C)

Measure Description

To be summarized using descriptive statistics.

Time Frame

Through 30-37 days following the last dose of DV; up to approximately 2 years

Outcome Measure

PK parameter of pembrolizumab - Cmax (Cohort E)

Measure Description

To be summarized using descriptive statistics.

Time Frame

Through 30-37 days following the last dose of DV; up to approximately 2 years

Outcome Measure

Incidence of anti-drug antibodies (ADAs) against disitamab vedotin (All Cohorts)

Measure Description

To be summarized using descriptive statistics.

Time Frame

Through 30-37 days following the last dose of DV; up to approximately 2 years

Outcome Measure

Incidence of anti-drug antibodies (ADAs) against pembrolizumab (Cohorts C and E)

Measure Description

To be summarized using descriptive statistics.

Time Frame

Through 30-37 days following the last dose of DV; up to approximately 2 years

Outcome Measure

Incidence of neutralizing antibodies (NABs) against disitamab vedotin (All Cohorts)

Measure Description

To be summarized using descriptive statistics.

Time Frame

Through 30-37 days following the last dose of DV; up to approximately 2 years

Secondary Outcome Measures table for Clinical Trial

Number of participants

332

Collaborators and investigators

Sponsor: Seagen Inc.

Collaborator: Merck Sharp & Dohme LLC

This information is current as of September 24th 2024.
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More Information Close NCT# stands for National Clinical Trial number. This is a unique identification code given to each clinical trial registered on ClinicalTrials.gov. The format is "NCT" followed by an 8-digit number (for example, NCT00000419). Also called the ClinicalTrials.gov identifier. NCT04879329