A Study of Disitamab Vedotin Alone or with Pembrolizumab in Urothelial Cancer That Expresses HER2
- Conditions
- Urothelial carcinoma
- Interventions
- Registration Number
- 2022-500030-28-01
- Lead Sponsor
- Seagen Inc.
- Brief Summary
To evaluate the efficacy as measured by cORR assessed by BICR for disitamab vedotin monotherapy in previously treated participants with LA/mUC that expresses HER2 (HER2-positive [IHC 3+, or IHC 2+ and ISH-positive], and HER2-low [IHC 2+ and ISH-negative, or IHC 1+])
To evaluate the efficacy as measured by cORR assessed by BICR for disitamab vedotin alone and combined with pembrolizumab in treatment-naive participants with LA/mUC that expresses HER2
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Not specified
- Target Recruitment
- 14
Expected survival ≥12 weeks
Locally-advanced unresectable or metastatic (American Joint Commission on Cancer Stages TNM Stage IIIB–IV [Amin 2017]) UC with histopathological confirmation, including UC originating from the renal pelvis, ureters, bladder, or urethra. Mixed-cell type tumors are eligible as long as urothelial (transitional cell) carcinoma is the predominant cell type.
Prior therapy: a.Participantsmust have received only 1 or 2 lines of prior systemic therapy for LA/mUC, including 1 line of platinum-containing chemotherapy. i.Neoadjuvant or adjuvant systemic therapy, with progression within 12 months of completing final dose of therapy, is considered as one line of prior therapy. ii.Maintenance avelumab therapy delivered following first-line platinum therapy is not considered a separate line of therapy. iii.Prior therapy with PD-(L)1 inhibitors as (neo)adjuvant therapy, first-line maintenance therapy or as second-line treatment is allowed.
Radiographically documented disease progression during or after the most recent line of therapy for LA/mUC
At least one measurable lesion by investigator assessment based on RECIST version 1.1.
Participants must be willing and able to provide archived (formalin-fixed paraffin-embedded tumor tissue blocks (or alternatively freshly sectioned slides; see laboratory manual for details and Section 7.1.3). This must be obtained prior to study treatment initiation and will be sent to a sponsor-designated central laboratory for biomarker analysis. If archival tissue is not available, then a newly obtained baseline biopsy of an accessible tumor lesion is required within 28 days prior to the Cycle 1 Day 1. Biopsy must provide adequate tissue for HER2 testing.
HER2-expression status determined by the central laboratory to be IHC 1+, 2+ or 3+, on the provided tumor tissue sample of muscle-invasive or metastatic UC.
Participants must have an ECOG performance status of 0 or 1.
Known hypersensitivity to disitamab vedotin or any of their components
Received antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc.) or participated in another clinical study within 2 weeks prior to the start of the 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
Received live or live-attenuated vaccines within 4 weeks prior to study treatment initiation or plan on receiving such vaccines during the course of study treatment
Participants with acute, chronic or symptomatic infections, including: A. Ongoing symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. B. History of human immunodeficiency virus infection. C. History of hepatitis B virus (HBV) infection (defined as positive for HBV surface antigen) or known active hepatitis C virus (HCV) infection (defined as HCV RNA [qualitative] is detected).
Other serious, uncontrolled concomitant diseases that may affect protocol compliance or interpretation of outcomes, including active opportunistic infections or advanced (severe) infections, or uncontrolled diabetes.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort A - DV monotherapy for HER2-positive tumor types disitamab vedotin Disitamab vedotin monotherapy Cohort B - DV monotherapy for HER2-low tumor types disitamab vedotin Disitamab vedotin monotherapy Cohort C - Non-randomized combination therapy disitamab vedotin Disitamab vedotin + pembrolizumab Cohort C - Non-randomized combination therapy pembrolizumab Disitamab vedotin + pembrolizumab Cohort C - Randomized combination therapy disitamab vedotin Disitamab vedotin + pembrolizumab Cohort C - Randomized combination therapy pembrolizumab Disitamab vedotin + pembrolizumab Cohort C - Randomized monotherapy disitamab vedotin Disitamab vedotin monotherapy Cohort D - DV monotherapy (Japan only) disitamab vedotin Disitamab vedotin monotherapy Cohort E - DV combination therapy (Japan only) disitamab vedotin Disitamab vedotin + pembrolizumab Cohort E - DV combination therapy (Japan only) pembrolizumab Disitamab vedotin + pembrolizumab Cohort G - DV monotherapy disitamab vedotin Disitamab vedotin
- Primary Outcome Measures
Name Time Method cORR (confirmed CR and confirmed PR) per RECIST v1.1 as assessed by BICR cORR (confirmed CR and confirmed PR) per RECIST v1.1 as assessed by BICR
cORR per RECIST v1.1 as assessed by BICR cORR per RECIST v1.1 as assessed by BICR
- Secondary Outcome Measures
Name Time Method cORR per RECIST v1.1, as assessed by the investigator cORR per RECIST v1.1, as assessed by the investigator
Confirmed DOR per RECIST v1.1, as assessed by BICR ● Confirmed DOR per RECIST v1.1, as assessed by the investigator Confirmed DOR per RECIST v1.1, as assessed by BICR ● Confirmed DOR per RECIST v1.1, as assessed by the investigator
PFS per RECIST v1.1, as assessed by BICR ● PFS per RECIST v1.1, as assessed by the investigator PFS per RECIST v1.1, as assessed by BICR ● PFS per RECIST v1.1, as assessed by the investigator
DCR (confirmed CR, confirmed PR, and stable disease) per RECIST v1.1, as assessed by BICR ● DCR per RECIST v1.1, as assessed by the investigator DCR (confirmed CR, confirmed PR, and stable disease) per RECIST v1.1, as assessed by BICR ● DCR per RECIST v1.1, as assessed by the investigator
OS OS
Type, incidence, relatedness, severity and seriousness of AEs ● Treatment discontinuations, dose reductions, or dose delays due to AEs ● Type, incidence and severity of laboratory abnormalities ● ECG abnormalities, including changes in QTc ● Effect on LVEF Type, incidence, relatedness, severity and seriousness of AEs ● Treatment discontinuations, dose reductions, or dose delays due to AEs ● Type, incidence and severity of laboratory abnormalities ● ECG abnormalities, including changes in QTc ● Effect on LVEF
PK parameters of disitamab vedotin, free MMAE, and TAb PK parameters of disitamab vedotin, free MMAE, and TAb
Incidence of ADA and NABs against disitamab vedotin Incidence of ADA and NABs against disitamab vedotin
Trial Locations
- Locations (161)
Banner Gateway Medical Center
🇺🇸Gilbert, Arizona, United States
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Kaiser Permanente Anaheim Kraemer Medical Offices
🇺🇸Anaheim, California, United States
Kaiser Permanente Baldwin Park Medical Center
🇺🇸Baldwin Park, California, United States
Kaiser Permanente Bellflower Medical Offices
🇺🇸Bellflower, California, United States
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
🇺🇸Duarte, California, United States
Kaiser Permanente Fontana Medical Center
🇺🇸Fontana, California, United States
Kaiser Permanente South Bay Medical center
🇺🇸Harbor City, California, United States
Chao Family Comprehensive Cancer Center and Ambulatory Care
🇺🇸Irvine, California, United States
UCI Health - Irvine Infusion Pharmacy ACC
🇺🇸Irvine, California, United States
Scroll for more (151 remaining)Banner Gateway Medical Center🇺🇸Gilbert, Arizona, United States