Trial Title:
A Study of Efficacy and Safety of Sacituzumab Tirumotecan (MK-2870) Plus Enfortumab Vedotin (EV) With and Without Pembrolizumab in Advanced Urothelial Carcinoma (MK-3475-04C/KEYMAKER-U04)
NCT ID:
NCT06483334
Condition:
Metastatic Urothelial Carcinoma
Locally Advanced Urothelial Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Transitional Cell
Pembrolizumab
Conditions: Keywords:
Programmed Cell Death-1 (PD1, PD-1)
Programmed Cell Death 1 Ligand 1(PDL1, PD-L1)
Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Part 1 is non-randomized open-label. Part 2 is randomized open-label.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Sacituzumab tirumotecan
Description:
IV infusion at different dose levels
Arm group label:
Sacituzumab tirumotecan plus EV
Arm group label:
Sacituzumab tirumotecan plus EV and pembrolizumab
Other name:
MK-2870
Other name:
SKB264
Intervention type:
Biological
Intervention name:
Enfortumab Vedotin
Description:
IV infusion at different dose levels
Arm group label:
Sacituzumab tirumotecan plus EV
Arm group label:
Sacituzumab tirumotecan plus EV and pembrolizumab
Other name:
PADCEV™
Intervention type:
Biological
Intervention name:
Pembrolizumab
Description:
200 mg IV infusion
Arm group label:
Sacituzumab tirumotecan plus EV and pembrolizumab
Other name:
MK-3475
Other name:
KEYTRUDA
Summary:
This study is a substudy being conducted under one pembrolizumab umbrella master study
KEYMAKER-U04. The substudy will consist of 2 parts. Part 1 will evaluate the safety and
preliminary efficacy of sacituzumab tirumotecan plus enfortumab vedotin (EV). Part 2 will
be based on Part 1 results and will evaluate the efficacy, pharmacokinetics, and safety
of sacituzumab tirumotecan plus EV in combination with pembrolizumab in participants with
advanced urothelial carcinoma.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
- Must have histologically documented, locally advanced/metastatic urothelial
carcinoma (la/mUC).
- Must provide an archival tumor tissue sample or newly obtained core or excisional
biopsy of a tumor lesion demonstrating UC, not previously irradiated, and adequate
for biomarker evaluation. A newly obtained biopsy is strongly preferred, but not
required if archival tissue is evaluable.
- Any AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or
baseline. Endocrine-related AEs adequately treated with hormone replacement are
eligible.
- PART 1 ONLY: Participants must have received platinum-based chemotherapy for
treatment of la/mUC.
- PART 1 ONLY: Participants must not have received >2 lines of therapy for la/mUC.
Platinum-based chemotherapy followed by avelumab maintenance is considered 2 lines
of therapy.
- PART 2 ONLY: Participants must not have received prior systemic therapy for la/mUC.
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
- Known additional malignancy that is progressing or has required active treatment
within the past 3 years.
- Known active central nervous system metastases and/or carcinomatous meningitis.
- Has Grade ≥2 peripheral neuropathy.
- Has history of documented severe dry eye syndrome, severe Meibomian gland disease
and/or blepharitis, or corneal disease that prevents/delays corneal healing.
- Has active inflammatory bowel disease requiring immunosuppressive medication or
previous history of inflammatory bowel disease (eg, Crohn's disease, ulcerative
colitis, or chronic diarrhea).
- Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
and/or serious cardiovascular and cerebrovascular diseases within the 6 months
preceding study intervention.
- Has active keratitis or corneal ulcerations. Superficial punctate keratitis is
allowed if the disorder is being adequately treated in the opinion of the
investigator.
- Has a history of uncontrolled diabetes.
- Has received an investigational agent or has used an investigational device within 4
weeks prior to study intervention administration.
- Has received a live or live-attenuated vaccine within 30 days prior to the first
dose of study intervention.
- PART 2 ONLY: Has a diagnosis of immunodeficiency or is receiving chronic systemic
steroid therapy or any other form of immunosuppressive therapy within 7 days before
the first dose of study intervention. Inhaled or topical steroids are permitted in
the absence of active autoimmune disease. Physiologic replacement doses of
corticosteroids are permitted for participants with adrenal insufficiency.
- PART 2 ONLY: Has an active autoimmune disease that has required systemic treatment
in past 2 years except replacement therapy. - Is human immunodeficiency virus
(HIV)-infected and has a history of Kaposi's sarcoma and/or Multicentric Castleman's
Disease.
- Has active Hepatitis B or Hepatitis C virus infection.
- Has a history of (noninfectious) pneumonitis/interstitial lung disease that required
steroids or has current pneumonitis/interstitial lung disease.
- Has an active infection requiring systemic therapy.
- PART 2 ONLY: History of allogeneic tissue/solid organ transplant.
- Has not adequately recovered from major surgery or has ongoing surgical
complications.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Siteman Cancer Center ( Site 4038)
Address:
City:
Saint Louis
Zip:
63108
Country:
United States
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
314-362-5740
Facility:
Name:
Cleveland Clinic-Taussig Cancer Center ( Site 4036)
Address:
City:
Cleveland
Zip:
44195
Country:
United States
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
216-444-8311
Facility:
Name:
Huntsman Cancer Institute-HCI Clinical Trials Office ( Site 4041)
Address:
City:
Salt Lake City
Zip:
84112
Country:
United States
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
801-213-8439
Facility:
Name:
The Ottawa Hospital - General Campus ( Site 4105)
Address:
City:
Ottawa
Zip:
K1H 8L6
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
6137377700
Facility:
Name:
Rambam Health Care Campus ( Site 4501)
Address:
City:
Haifa
Zip:
3109601
Country:
Israel
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
97247776750
Facility:
Name:
Rabin Medical Center-Oncology ( Site 4504)
Address:
City:
Petah Tikva
Zip:
4941492
Country:
Israel
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
+972-39378074
Facility:
Name:
Sheba Medical Center-ONCOLOGY ( Site 4503)
Address:
City:
Ramat Gan
Zip:
5265601
Country:
Israel
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
0525505090
Facility:
Name:
Severance Hospital, Yonsei University Health System-Medical oncology ( Site 4903)
Address:
City:
Seoul
Zip:
03722
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
82222288138
Facility:
Name:
Asan Medical Center-Department of Oncology ( Site 4901)
Address:
City:
Seoul
Zip:
05505
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
82230105977
Facility:
Name:
Samsung Medical Center ( Site 4902)
Address:
City:
Seoul
Zip:
06351
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
82234101767
Facility:
Name:
Nederlands Kanker Instituut - Antoni van Leeuwenhoek - NKI-AVL ( Site 4302)
Address:
City:
Amsterdam
Zip:
1066 CX
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
31205122569
Facility:
Name:
St Bartholomew s Hospital ( Site 4206)
Address:
City:
London
Zip:
EC1A 7BE
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
020 7822 8498
Start date:
July 17, 2024
Completion date:
July 28, 2028
Lead sponsor:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Source:
Merck Sharp & Dohme LLC
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06483334
https://www.merckclinicaltrials.com/
https://trialstransparency.merckclinicaltrials.com/Study.aspx?id=3475-04C&&kw=3475-04C
