A Study of Disitamab Vedotin Alone or With Pembrolizumab in Urothelial Cancer That Expresses HER2
- Conditions
- Interventions
- Registration Number
- NCT04879329
- Lead Sponsor
- Seagen Inc.
- Brief Summary
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.
...
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 332
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
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort B - DV monotherapy for HER2-low tumor types disitamab vedotin Disitamab vedotin monotherapy Cohort C - Randomized combination therapy disitamab vedotin Disitamab vedotin + pembrolizumab Cohort C - Randomized monotherapy disitamab vedotin Disitamab vedotin monotherapy Cohort A - DV monotherapy for HER2-positive tumor types disitamab vedotin Disitamab vedotin monotherapy Cohort C - Non-randomized combination therapy disitamab vedotin Disitamab vedotin + pembrolizumab Cohort E - DV combination therapy (Japan only) pembrolizumab Disitamab vedotin + pembrolizumab Cohort C - Non-randomized combination therapy pembrolizumab Disitamab vedotin + pembrolizumab Cohort C - Randomized combination therapy pembrolizumab Disitamab vedotin + pembrolizumab Cohort D - DV monotherapy (Japan only) disitamab vedotin Disitamab vedotin monotherapy Cohort E - DV combination therapy (Japan only) disitamab vedotin Disitamab vedotin + pembrolizumab
- Primary Outcome Measures
Name Time Method Incidence of laboratory abnormalities (Cohorts D and E) Approximately 2 years To be summarized using descriptive statistics.
Incidence of dose alterations (Cohorts D and E) Approximately 2 years Incidence of electrocardiogram (ECG) abnormalities (Cohorts D and E) Approximately 2 years Change from baseline of left ventricular ejection fraction (LVEF) (Cohorts D and E) Approximately 2 years PK parameter - Time to maximum concentration (Tmax) (Cohorts D and E) Through 30-37 days following the last dose of DV; up to approximately 2 years To be summarized using descriptive statistics.
PK parameter - Trough concentration (Ctrough) (Cohorts D and E) Through 30-37 days following the last dose of DV; up to approximately 2 years To be summarized using descriptive statistics.
Incidence of adverse events (AEs) (Cohorts D and E) Approximately 2 years 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.
Pharmacokinetic (PK) parameter - Area under the curve (AUC) (Cohorts D and E) Through 30-37 days following the last dose of DV; up to approximately 2 years To be summarized using descriptive statistics.
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) Duration of treatment; approximately 2 years The proportion of participants with confirmed complete response (CR) or partial response (PR) according to RECIST v1.1
PK parameter - Maximum concentration (Cmax) (Cohorts D and E) Through 30-37 days following the last dose of DV; up to approximately 2 years To be summarized using descriptive statistics.
- Secondary Outcome Measures
Name Time Method Confirmed Duration of Response (DOR) per RECIST v1.1 by BICR (Cohorts A, B, and C) From start of treatment to completion of response assessment; approximately 2 years 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.
Change from baseline of LVEF (Cohorts A, B, and C) Approximately 2 years PFS per RECIST v1.1 by investigator assessment (Cohorts A, B, and C) From start of treatment to completion of response assessment; approximately 2 years 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.
Overall survival (OS) (Cohorts A, B, and C) Duration of study; approximately 3 years The time from start of study treatment or randomization (if applicable) to the date of death due to any cause.
Incidence of ECG abnormalities (Cohorts A, B, and C) Approximately 2 years Incidence of anti-drug antibodies (ADAs) against disitamab vedotin (All Cohorts) Through 30-37 days following the last dose of DV; up to approximately 2 years To be summarized using descriptive statistics.
cORR per RECIST v1.1 by investigator assessment (Cohorts A, B, and C) Duration of treatment; approximately 2 years The proportion of participants with confirmed CR or PR according to RECIST v1.1
DCR per RECIST v1.1 by investigator (Cohorts A, B, and C) From start of treatment to completion of response assessment; approximately 2 years 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.
Incidence of laboratory abnormalities (Cohorts A, B, and C) Approximately 2 years To be summarized using descriptive statistics.
PK parameter - AUC (Cohorts A, B, and C) Through 30-37 days following the last dose of DV; up to approximately 2 years To be summarized using descriptive statistics.
PK parameter - Tmax (Cohorts A, B, and C) Through 30-37 days following the last dose of DV; up to approximately 2 years To be summarized using descriptive statistics.
PK parameter of pembrolizumab - Cmax (Cohort E) Through 30-37 days following the last dose of DV; up to approximately 2 years To be summarized using descriptive statistics.
Disease control rate (DCR) per RECIST v1.1 by BICR (Cohorts A, B, and C) From start of treatment to completion of response assessment; approximately 2 years 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.
Confirmed DOR per RECIST v1.1 by investigator assessment (Cohorts A, B, and C) From start of treatment to completion of response assessment; approximately 2 years 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.
Progression-free survival (PFS) per RECIST v1.1 by BICR (Cohorts A, B, and C) From start of treatment to completion of response assessment; approximately 2 years 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.
Incidence of dose alterations (Cohorts A, B, and C) Approximately 2 years To be summarized using descriptive statistics.
PK parameter - Ctrough (Cohorts A, B, and C) Through 30-37 days following the last dose of DV; up to approximately 2 years To be summarized using descriptive statistics.
Incidence of anti-drug antibodies (ADAs) against pembrolizumab (Cohorts C and E) Through 30-37 days following the last dose of DV; up to approximately 2 years To be summarized using descriptive statistics.
Incidence of neutralizing antibodies (NABs) against disitamab vedotin (All Cohorts) Through 30-37 days following the last dose of DV; up to approximately 2 years To be summarized using descriptive statistics.
Incidence of adverse events (AEs) (Cohorts A, B, and C) Approximately 2 years 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.
PK parameter - Cmax (Cohorts A, B, and C) Through 30-37 days following the last dose of DV; up to approximately 2 years To be summarized using descriptive statistics.
Trial Locations
- Locations (82)
GenesisCare North Shore (Oncology)
🇦🇺St Leonards, Other, Australia
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
City of Hope
🇺🇸Duarte, California, United States
University of California Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
University of California Irvine Medical Center
🇺🇸Orange, California, United States
Kaiser Permanente Southern California
🇺🇸Riverside, California, United States
University of California, San Francisco | HDFCCC - Hematopoietic Malignancies
🇺🇸San Francisco, California, United States
University of Colorado Health Memorial Hospital
🇺🇸Colorado Springs, Colorado, United States
MedStar Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
Florida Cancer Specialists - South Region
🇺🇸Fort Myers, Florida, United States
Florida Cancer Specialists - Panhandle
🇺🇸Tallahassee, Florida, United States
H. Lee Moffitt Cancer Center and Research Institute
🇺🇸Tampa, Florida, United States
Florida Cancer Specialists - East West Palm Beach, FL (SCRI)
🇺🇸West Palm Beach, Florida, United States
Northwest Georgia Oncology Centers, P.C.
🇺🇸Marietta, Georgia, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Karmanos Cancer Institute / Wayne State University
🇺🇸Detroit, Michigan, United States
Cancer and Hematology Centers of Western Michigan / Spectrum Health Butterworth Campus
🇺🇸Grand Rapids, Michigan, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
North Shore Center for Advanced Medicine Monter Cancer Center / North Shore University Hospital
🇺🇸Lake Success, New York, United States
New York University (NYU) Cancer Institute
🇺🇸New York, New York, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Oklahoma University at Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
University of Tennessee
🇺🇸Knoxville, Tennessee, United States
MD Anderson Cancer Center / University of Texas
🇺🇸Houston, Texas, United States
Baylor Scott & White Medical Center
🇺🇸Temple, Texas, United States
Huntsman Cancer Institute/University of Utah
🇺🇸Salt Lake City, Utah, United States
Inova Schar Cancer Institute
🇺🇸Fairfax, Virginia, United States
Fred Hutchinson Cancer Center / Seattle Cancer Care Alliance / University of Washington
🇺🇸Seattle, Washington, United States
Medical College of Wisconsin (Milwaukee)
🇺🇸Milwaukee, Wisconsin, United States
Centro de Oncologia e Investigacion de Buenos Aires (COIBA)
🇦🇷Berazategui, Other, Argentina
Hospital Aleman (HA) Deutsches Hospital
🇦🇷Buenos Aires, Other, Argentina
Hospital Sirio Libanes
🇦🇷Caba, Other, Argentina
Instituto Alexander Fleming
🇦🇷Ciudad Autonoma Buenos Aires, Other, Argentina
Instituto Oncologico de Cordoba
🇦🇷Cordoba, Other, Argentina
Fundacion Cenit
🇦🇷Caba, Argentina
Clinica Viedma
🇦🇷Viedma, Argentina
Lyell McEwin Hospital
🇦🇺Elizabeth Vale, Other, Australia
Peninsula and South East Oncology
🇦🇺Frankston, Other, Australia
Mater Cancer Care Centre
🇦🇺South Brisbane, Other, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Other, Australia
Sapporo Medical University Hospital
🇯🇵Sapporo, Other, Japan
Macquarie University Hospital
🇦🇺New South Whales, Australia
Algemeen Ziekenhuis Maria Middelares
🇧🇪Gent, Other, Belgium
CHU UCL Namur-Site de Saint Elisabeth
🇧🇪Namur, Other, Belgium
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
British Columbia Cancer Agency - Vancouver Centre
🇨🇦Vancouver, British Columbia, Canada
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
Centre hospitalier universitaire de Sherbrooke (CHUS)
🇨🇦Sherbrooke, Quebec, Canada
Centro de Estudios Clinicos IC La Serena Research
🇨🇱La Serena, Other, Chile
Pontificia Universidad Catolica De Chile Santiago
🇨🇱Santiago, Other, Chile
Instituto Oncologico Fundacion Arturo Lopez Perez (FALP)
🇨🇱Santiago, Other, Chile
Rambam Health Corp.
🇮🇱Haifa, Other, Israel
Rabin Medical Center
🇮🇱Petach Tikva, Other, Israel
Sheba Medical Center
🇮🇱Ramat Gan, Other, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Other, Israel
Policlinico Universitario Agostino Gemelli
🇮🇹Roma, Other, Italy
National Cancer Center Hospital East
🇯🇵Kashiwa-shi, Other, Japan
Osaka International Cancer Institute
🇯🇵Osaka, Other, Japan
Osaka University Hospital
🇯🇵Suita-shi, Other, Japan
Tokushima University Hospital
🇯🇵Tokushima, Other, Japan
The Cancer Institute Hospital of JFCR
🇯🇵Tokyo, Other, Japan
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Other, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Other, Spain
MD Anderson Cancer Center - Madrid
🇪🇸Madrid, Other, Spain
Hospital Universitari Parc Tauli
🇪🇸Sabadell, Other, Spain
Hospital Universitario Marques de Valdecilla
🇪🇸Santander, Other, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Seville, Other, Spain
The Clatterbridge Cancer Centre NHS Foundation Trust
🇬🇧Bebington, Other, United Kingdom
Cambridge University Hospitals NHS Foundation Trust
🇬🇧Cambridge, Other, United Kingdom
NHS Greater Glasgow and Clyde (NHSGGC) - The Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, Other, United Kingdom
Barts Health NHS Trust Saint Bartholomews Hospital
🇬🇧London, Other, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, Other, United Kingdom
Guys and St Thomas Hospital
🇬🇧London, United Kingdom
Imperial College Healthcare NHS Trust
🇬🇧London, United Kingdom