Disitamab Vedotin + Pembrolizumab for Bladder Cancer
Recruiting in Palo Alto (17 mi)
+86 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Seagen, a wholly owned subsidiary of Pfizer
Must not be taking: MMAE-based ADCs, HER2-directed
Disqualifiers: Immunodeficiency, Chronic steroids, Neuropathy, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial is testing a new drug called disitamab vedotin, alone or with pembrolizumab, for patients with advanced or metastatic HER2 expressing bladder cancer. Disitamab vedotin is designed to target HER2 and has been approved for other types of cancer. The study aims to see if these drugs can effectively treat the cancer and what side effects they might cause.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, it mentions that prior antitumor treatments should not have been received within 2 weeks before starting the study, which might imply a need to pause certain treatments. It's best to discuss your specific medications with the study center.
What data supports the effectiveness of the drug combination Disitamab Vedotin and Pembrolizumab for bladder cancer?
Disitamab Vedotin has shown effectiveness in treating HER2-positive metastatic urothelial carcinoma, and Pembrolizumab is approved for certain types of bladder cancer, indicating potential benefits when used together for bladder cancer treatment.
12345Is the combination of Disitamab Vedotin and Pembrolizumab safe for humans?
Pembrolizumab, also known as Keytruda, has been used in various studies for bladder cancer and other conditions, showing it can cause some side effects like asthma as an immune-related reaction. While it has been approved for certain types of bladder cancer, it's important to discuss potential risks with your doctor.
23678What makes the drug combination of Disitamab Vedotin and Pembrolizumab unique for bladder cancer?
This drug combination is unique because it combines Disitamab Vedotin, an antibody-drug conjugate targeting cancer cells, with Pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer. This approach may offer a novel way to treat bladder cancer by using two different mechanisms to target the disease.
256910Eligibility Criteria
This trial is for adults with advanced urothelial cancer that expresses HER2 and can't be removed by surgery or has spread. They should have had certain prior treatments, including platinum chemotherapy and PD-(L)1 inhibitors. Participants need to have at least one measurable tumor lesion, an ECOG performance status of 0-2, and no recent other cancer therapies.Inclusion Criteria
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 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
At least one measurable lesion by investigator assessment based on RECIST v1.1.
+21 more
Exclusion Criteria
I haven't had cancer treatment in the last 2 weeks.
I am not allergic to disitamab vedotin, pembrolizumab, or their ingredients.
I have not had treatments targeting specific immune system receptors.
+13 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive disitamab vedotin alone or in combination with pembrolizumab to treat HER2 expressing urothelial cancer
Approximately 2 years
Follow-up
Participants are monitored for safety and effectiveness after treatment
4-6 weeks
Long-term follow-up
Participants are monitored for long-term outcomes such as overall survival and adverse events
Approximately 3 years
Participant Groups
The study tests disitamab vedotin alone or combined with pembrolizumab in treating HER2 expressing urothelial cancer. It aims to evaluate the effectiveness and safety of these drugs in patients whose cancer is locally advanced or metastatic.
8Treatment groups
Experimental Treatment
Group I: Cohort G - DV monotherapyExperimental Treatment1 Intervention
Disitamab vedotin
Group II: Cohort E - DV combination therapy (Japan only)Experimental Treatment2 Interventions
Disitamab vedotin + pembrolizumab
Group III: Cohort D - DV monotherapy (Japan only)Experimental Treatment1 Intervention
Disitamab vedotin monotherapy
Group IV: Cohort C - Randomized monotherapyExperimental Treatment1 Intervention
Disitamab vedotin monotherapy
Group V: Cohort C - Randomized combination therapyExperimental Treatment2 Interventions
Disitamab vedotin + pembrolizumab
Group VI: Cohort C - Non-randomized combination therapyExperimental Treatment2 Interventions
Disitamab vedotin + pembrolizumab
Group VII: Cohort B - DV monotherapy for HER2-low tumor typesExperimental Treatment1 Intervention
Disitamab vedotin monotherapy
Group VIII: Cohort A - DV monotherapy for HER2-positive tumor typesExperimental Treatment1 Intervention
Disitamab vedotin monotherapy
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
New York University (NYU) Cancer InstituteNew York, NY
Ohio State UniversityColumbus, OH
Oklahoma University at Stephenson Cancer CenterOklahoma City, OK
Baylor Scott & White Medical CenterTemple, TX
More Trial Locations
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Who Is Running the Clinical Trial?
Seagen, a wholly owned subsidiary of PfizerLead Sponsor
Seagen Inc.Lead Sponsor
Merck Sharp & Dohme LLCIndustry Sponsor
RemeGen Co., Ltd.Industry Sponsor
References
HER2-targeting antibody-drug conjugate RC48 alone or in combination with immunotherapy for locally advanced or metastatic urothelial carcinoma: a multicenter, real-world study. [2023]Phase II trials showed the efficacy of anti-HER2 RC48-ADC (disitamab vedotin) for HER2-positive metastatic urothelial carcinoma (UC). This study evaluated RC48 alone verses in combination with immunotherapy for locally advanced or metastatic UC using real-world data.
FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. [2021]The FDA approved pembrolizumab (Keytruda) for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or chose to not undergo cystectomy.
Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Urothelial Bladder Carcinoma (PURE-01): An Open-Label, Single-Arm, Phase II Study. [2021]To determine the activity of pembrolizumab as neoadjuvant immunotherapy before radical cystectomy (RC) for muscle-invasive bladder carcinoma (MIBC) for which standard cisplatin-based chemotherapy is poorly used.
Efficacy and Safety of Disitamab Vedotin in Patients With Human Epidermal Growth Factor Receptor 2-Positive Locally Advanced or Metastatic Urothelial Carcinoma: A Combined Analysis of Two Phase II Clinical Trials. [2023]To evaluate the efficacy and safety of disitamab vedotin (DV, RC48-ADC), a novel humanized anti-human epidermal growth factor receptor 2 (HER2) antibody conjugated with monomethyl auristatin E, in patients with HER2-positive locally advanced or metastatic urothelial carcinoma (UC) refractory to standard or regular therapies.
Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer. [2023]Patients with locally advanced or metastatic urothelial cancer (la/mUC) who are ineligible for cisplatin-based therapy have limited first-line (1L) treatment options and significant need for improved therapies. Enfortumab vedotin (EV) and pembrolizumab (Pembro) individually have shown a survival benefit in urothelial cancer in second-line + la/mUC settings. Here, we present data from the pivotal trial of EV plus Pembro (EV + Pembro) in the 1L setting.
Pembrolizumab in the treatment of advanced urothelial cancer. [2018]Pembrolizumab is a humanized monoclonal antibody that targets PD-1. In the Phase III trial KEYNOTE-045, pembrolizumab was associated with a significant overall survival benefit when compared with docetaxel, paclitaxel and vinflunine in second line metastatic urothelial carcinoma (UC). Additionally, in the first line, early results from an interim analysis of the Phase II trial Keynote-052 study indicated that pembrolizumab is efficacious for cisplatin-ineligible patients. Based on data from these trials, pembrolizumab was the most recent among the five checkpoint inhibitors tested in UC to be approved by the US FDA in May 2017. It was granted regular approval for patients with advanced-stage UC who progress after receiving platinum-based chemotherapy and accelerated approval in the first line for patients who are ineligible to receive cisplatin.
Cost-effectiveness of Pembrolizumab for Patients with Advanced, Unresectable, or Metastatic Urothelial Cancer Ineligible for Cisplatin-based Therapy. [2022]There is an unmet need for effective therapies for patients with advanced or metastatic urothelial cancer who cannot tolerate cisplatin-based chemotherapy. Cisplatin-ineligible patients experience a high frequency of adverse events from the most commonly used standard of care treatment, carboplatin plus gemcitabine, or alternative treatment with gemcitabine monotherapy. Pembrolizumab is a potent, highly selective humanised monoclonal antibody that releases checkpoint inhibition of the immune response system, and provides a new alternative for these patients.
A case of bronchial asthma as an immune-related adverse event of pembrolizumab treatment for bladder cancer: A case report. [2022]Bladder cancer is one of the most common cancers worldwide. The anti-programmed cell death protein 1 (PD-1) antibody pembrolizumab, which is an immune checkpoint inhibitor (ICI), has improved survival in bladder cancer. We report a case of bladder cancer that had a high antitumor effect with anti-programmed cell death PD-1 antibody pembrolizumab, an ICI, but asthma occurred an immune-related adverse event (irAE).
Clinicopathologic and Genomic Characterization of PD-L1 Positive Urothelial Carcinomas. [2021]Pembrolizumab was approved with an accompanying companion diagnostic (CDx) assay (PD-L1 DAKO 22C3) for urothelial carcinoma (UC). In this study, we further characterize the clinicopathologic and genomic features of UC that are programmed death-ligand 1 (PD-L1) positive.
A plain language summary exploring a new treatment combination for untreated locally advanced or metastatic urothelial cancer: enfortumab vedotin plus pembrolizumab. [2023]This summary provides the results of a study of two treatments for cancer, enfortumab vedotin and pembrolizumab, that were studied together against locally advanced or metastatic urothelial cancer (la/mUC), a cancer that occurs most commonly in the bladder.