Disitamab Vedotin With Pembrolizumab vs Chemotherapy in Previously Untreated Urothelial Cancer Expressing HER2

Urothelial Carcinoma Clinical Trial

Official title:

An Open-label, Randomized, Controlled Phase 3 Study of Disitamab Vedotin in Combination With Pembrolizumab Versus Chemotherapy in Subjects With Previously Untreated Locally Advanced or Metastatic Urothelial Carcinoma That Expresses HER2 (IHC 1+ and Greater)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05911295
• Other study ID #: SGNDV-001
• Secondary ID: KEYNOTE-D74MK-34
• Status: Recruiting
• Phase: Phase 3
• Start date: September 22, 2023
• Est. completion date: April 30, 2029

Study information

• Verified date: May 2024
• Source: Seagen Inc.
• Contact: Seagen Trial Information Support
• Phone: 866-333-7436
• Email: clinicaltrials[@]seagen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will enroll participants with urothelial cancer (UC). UC can include cancer of the bladder, kidney, or the tubes that carry pee through the body (ureter, urethra). This study will try to find out if the drugs disitamab vedotin with pembrolizumab works better than platinum-containing chemotherapy to treat patients with UC. This study will also test what side effects happen when participants take these drugs together. A side effect is anything a drug does to the body besides treating the disease. Participants in this study will have cancer that has spread through the body (metastatic) or spread near where it started (locally advanced). In this study, there are 2 different groups. Participants will be assigned to a group randomly. Participants in the disitamab vedotin arm will get the study drug disitamab vedotin once every two weeks and pembrolizumab once every 6 weeks. Participants in the standard of care arm will get gemcitabine once a week for 2 weeks with either cisplatin or carboplatin once every 3 weeks.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 700
• Est. completion date: April 30, 2029
• Est. primary completion date: June 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histopathological confirmation of locally advanced unresectable or metastatic urothelial carcinoma (LA/mUC), including UC originating from the renal pelvis, ureters, bladder, or urethra.
• Measurable disease by investigator assessment per RECIST v1.1.
• Participant must not have received prior systemic therapy for LA/mUC. Exception will be made for neoadjuvant or adjuvant therapy, if disease recurrence/progression occurred more than 12 months after the last dose of therapy.
• Eligible to receive cisplatin- or carboplatin-containing chemotherapy.
• Able to provide archived formalin-fixed paraffin-embedded tumor tissue blocks from a muscle-invasive or metastatic UC lesion or biopsy of metastatic UC prior to treatment initiation. If archival tissue is not available a newly obtained baseline biopsy of an accessible tumor lesion is required within 28 days of cycle 1 day 1.
• HER2 expression of 1+ or greater on immunohistochemistry (IHC).
• Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1, or 2 within 7 days prior to randomization.

Exclusion Criteria:

• Known hypersensitivity to disitamab vedotin, cisplatin, carboplatin, gemcitabine, or pembrolizumab or any of their components.
• History of severe/life threatening immune-related adverse event (irAE) with PD-(L)1 inhibitors are excluded.
• Central nervous system (CNS) and/or leptomeningeal metastasis. Participants with treated CNS metastases are permitted if all of the following are met.
• CNS metastases have been clinically stable for at least 4 weeks and baseline scans show no evidence of new or worsening CNS metastasis.
• Participant is on a stable dose of = 10 mg/day of prednisone or equivalent for at least 2 weeks.
• History of or active autoimmune disease that has required systemic treatment in the past 2 years.
• 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).
• Prior solid organ or bone marrow transplantation.
• Pleural effusion or ascites with symptoms or requiring symptomatic treatment.
• Estimated life expectancy <12 week
• Prior treatment with an MMAE agent or anti-HER2 therapy

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Urothelial Carcinoma

Intervention

Drug:
• disitamab vedotin
Given into the vein (IV; intravenous) every 2 weeks
• pembrolizumab
400mg given by IV every 6 weeks
• gemcitabine
1000 mg/m^2 given by IV on days 1 and 8 of every 3-week cycle
• cisplatin
70 mg^2 given by IV on day 1 of every 3-week cycle
• carboplatin
Area under the plasma concentration-time curve (AUC) 4.5 or 5 given by IV on day 1 of every 3-week cycle

Locations

Country	Name	City	State
Australia	Macquarie University Hospital	Brisbane	Other
Australia	Lyell McEwin Hospital	Elizabeth Vale	Other
Australia	Peninsula and South East Oncology	Frankston	Other
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Lakeridge Health - The R.S. McLaughlin Durham Regional Cancer Centre (MDRCC)	Oshawa	Ontario
Canada	University Health Network, Princess Margaret Hospital	Toronto	Other
Singapore	National Cancer Centre Singapore	Singapore	Other
United States	Alaska Oncology and Hematology	Anchorage	Alaska
United States	MidLantic Urology	Bala-Cynwyd	Pennsylvania
United States	The Oncology Institute of Hope & Innovation - California	Cerritos	California
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	Decatur Memorial Hospital - Illinois	Decatur	Illinois
United States	Providence Regional Medical Center Everett	Everett	Washington
United States	Compassionate Care Research Group	Fountain Valley	California
United States	West Cancer Center & Research Institute	Germantown	Tennessee
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	University of Tennessee	Knoxville	Tennessee
United States	North Shore Center for Advanced Medicine Monter Cancer Center / North Shore University Hospital	Lake Success	New York
United States	Cancer Partners of Nebraska	Lincoln	Nebraska
United States	University of California Los Angeles Medical Center	Los Angeles	California
United States	Medical College of Wisconsin (Milwaukee)	Milwaukee	Wisconsin
United States	Pacific Cancer Care	Monterey	California
United States	Mount Sinai Medical Center	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Illinois Cancer Care	Peoria	Illinois
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Kaiser Permanente Southern California	Riverside	California
United States	HealthPartners Institute	Saint Louis Park	Minnesota
United States	University of California, San Francisco | HDFCCC - Hematopoietic Malignancies	San Francisco	California
United States	Providence Medical Foundation	Santa Rosa	California
United States	Fred Hutchinson Cancer Center / Seattle Cancer Care Alliance / University of Washington	Seattle	Washington
United States	Siouxland Regional Cancer Center dba June E. Nylen Cancer Center	Sioux City	Iowa
United States	US Oncology Central Regulatory	The Woodlands	Texas
United States	PIH Health Hospital Whittier	Whittier	California

Sponsors (3)

Lead Sponsor	Collaborator
Seagen Inc.	Merck Sharp & Dohme LLC, RemeGen Co., Ltd.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review (BICR)	The time from randomization to first documentation of disease progression per RECIST v1.1 by BICR, or to death due to any cause.	Approximately 3 years
Primary	Overall survival (OS)	The time from date of randomization to date of death due to any cause.	Approximately 5 years
Secondary	Objective response rate (ORR) per RECIST v1.1 by BICR	The proportion of participants with confirmed complete response (CR) or partial response (PR) according to RECIST v1.1.	Approximately 3 years
Secondary	ORR per RECIST v1.1 by investigator assessment	The proportion of participants with confirmed CR or PR according to RECIST v1.1.	Approximately 3 years
Secondary	Duration of Response (DOR) per RECIST v1.1 by BICR	The time from first documented response of CR or PR (that is subsequently confirmed) to the first documented disease progression per RECIST v1.1, or to death due to any cause.	Approximately 3 years
Secondary	DOR per RECIST v1.1 by investigator assessment	The time from first documented response of CR or PR (that is subsequently confirmed) to the first documented disease progression per RECIST v1.1, or to death due to any cause.	Approximately 3 years
Secondary	Control Rate (DCR) per RECIST v1.1 by BICR	The proportion of participants with confirmed CR, PR, or stable disease according to RECIST v1.1.	Approximately 3 years
Secondary	DCR per RECIST v1.1 by investigator assessment	The proportion of participants with confirmed CR, PR, or stable disease according to RECIST v1.1.	Approximately 3 years
Secondary	PFS per RECIST v1.1 by investigator assessment	The time from randomization to first documentation of disease progression per RECIST v1.1, or to death due to any cause.	Approximately 3 years
Secondary	Number of participants with adverse events (AEs)	Any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	Through 30 days after the last study treatment; approximately 2 years
Secondary	Number of participants with laboratory abnormalities		Through 30 days after the last study treatment; approximately 2 years
Secondary	Treatment discontinuation rate due to AEs		Approximately 2 years
Secondary	Number of electrocardiogram (ECG) abnormalities		Through 30 days after the last study treatment; approximately 2 years
Secondary	Change from baseline of left ventricular ejection fraction (LVEF)		Through 2 years after last study treatment; approximately 4 years
Secondary	Change from baseline to Week 16 in European Organization for Research and Treatment of Cancer core Quality of Life questionnaire (EORTC QLQ-C30) Global Health Status (GHS)/QoL Score	The EORTC QLQ-C30 is used to evaluate health-related quality of life, functioning, disease symptoms, and treatment-related side effects. Scores range from 0-100. For GHS/QoL and functional scales, higher scores represent higher QoL or functioning. For symptom scales, higher scores represent more symptoms/worse status.	Approximately 2 years
Secondary	Time to Deterioration in EORTC QLQ-C30 GHS/QoL Score	The time from the date of randomization to the date of first deterioration (change from baseline =10) in GHS/QoL score with no subsequent recovery. The EORTC QLQ-C30 is used to evaluate health-related quality of life, functioning, disease symptoms, and treatment-related side effects. Scores range from 0-100. For GHS/QoL and functional scales, higher scores represent higher QoL or functioning. For symptom scales, higher scores represent more symptoms/worse status.	Approximately 2 years
Secondary	Time to pain progression	The time from the date of randomization to whichever of the following occurs earlier: an increase in Numeric Rating Scale (NRS) for pain intensity of 2 points or more from baseline at 2 consecutive visits,; an increase in number of opioid or analgesic use from baseline,; or initiation of opioid or analgesic use. NRS for pain intensity asks participants to best describe their pain at its worst in the last 24 hours from 0 to 10. On the NRS, 0 means no pain and 10 means pain as bad as you can imagine.	Approximately 2 years