Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Enfortumab vedotin (EV)
Enfortumab vedotin · 6 trials · 16 indications
PFS was defined as the time from date of randomization to first documentation of disease progression (PD), or to death due to any cause, whichever occurred first. PD: at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). PD could also be unequivocal progression of non-target lesions or the presence of unequivocal new lesions. Kaplan-Meier method was used for analysis.
OS was defined as the time from the date of randomization to the date of death from any cause. In the absence of death, OS was censored at the date the participant was last known to be alive. Kaplan-Meier method was used for analysis.
Clinical complete response rate will be defined as cT0 or cTa (low grade) disease at the time of restaging after 3 cycles of induction enfortumab vedotin plus pembrolizumab
Bladder-intact event-free survival (BI-EFS). The primary analysis will be performed after the last participant has completed at least 15 months of follow-up from the first dose of study treatment or when 21 BI-EFS events have been observed, whichever occurs first.
Will be assessed by the combination of partial response (PR) and complete response (CR). PR is defined as pathologic stage \<T2 disease. CR is defined as pT0 disease and assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1.
Will be measured by Response Evaluation Criteria in Solid Tumors version 1.1, and estimated by the Clopper-Pearson method with 95% confidence intervals.
Confirmed ORR was defined as the percentage of participants whose objective response was confirmed as CR or PR according to RECIST V1.1 per investigator assessment, using exact method based on binomial distribution (Clopper-Pearson).
Confirmed ORR was defined as the percentage of participants whose objective response was confirmed as CR or PR according to RECIST V1.1 per investigator assessment, using exact method based on binomial distribution (Clopper-Pearson).
| Arm | Type | Description |
|---|---|---|
| Arm A | EXPERIMENTAL | Enfortumab vedotin + pembrolizumab |
| Arm B | ACTIVE_COMPARATOR | Gemcitabine + cisplatin or carboplatin |
| Enfortumab vedotin plus pembrolizumab | EXPERIMENTAL | Patients with MIBC will receive 3 cycles (C1-C3) of induction enfortumab vedotin (1.25 mg/kg for a maximum dose of 125 mg) plus pembrolizumab (200 mg) followed by restaging including MRI of the bladder, urine cytology, and cystoscopy with TURBT of any visible tumor and/or resection site plus random biopsies using a recommended template. Patients achieving a stringently defined cCR (defined below) will receive 14 cycles of "maintenance" treatment. Enfortumab vedotin (1.25 mg/kg for a maximum dose of 125 mg) will be administered during the first 6 cycles (C4-C9) of "maintenance" treatment and pembrolizumab (200 mg) will be given all 14 cycles (C4-C14). Patients with any residual disease at clinical restaging (i.e., \>cTa disease) will undergo cystectomy. |
| After induction therapy and cCR: maintenance pembrolizumab only | EXPERIMENTAL | Patients receive four 3-weekly cycles of induction Enfortumab Vedotin on days 1, 8 and Pembrolizumab day 1. If, after tumor assessment, the response is deemed a cCR, patients can be randomized to this group. This arm will receive Pembrolizumab maintenance: 400 mg q6weeks. |
| After induction therapy and cCR: consolidative radiotherapy, followed by maintenance pembrolizumab. | EXPERIMENTAL | Patients receive four 3-weekly cycles of induction Enfortumab Vedotin on days 1, 8 and Pembrolizumab day 1. If, after tumor assessment, the response is deemed a cCR, patients can be randomized to this group. This arm will receive consolidative radiotherapy followed by Pembrolizumab maintenance: 400 mg q6weeks. |
| By residual disease may still receive bladder-sparing treatment | OTHER | Patients receive four 3-weekly cycles of induction Enfortumab Vedotin on days 1, 8 and Pembrolizumab day 1. If, after tumor assessment, the response is deemed a non-cCR, patients can be placed in this group. In this arm, patients may still receive bladder-sparing treatment using chemoradiotherapy (by local protocol; Mitomycin C/fluoropyrimidines in the Netherlands), followed by Pembrolizumab maintenance: 400 mg q6weeks. |
| By residual disease cannot receive bladder-sparing treatment | OTHER | Patients receive four 3-weekly cycles of induction Enfortumab Vedotin on days 1, 8 and Pembrolizumab day 1. If, after tumor assessment, the response is deemed a non-cCR, patients can be placed in this group. In this arm, patients will undergo a radical cystectomy, followed by Pembrolizumab maintenance: 400 mg q6weeks. |
| Treatment (pembrolizumab, enfortumab vedotin) | EXPERIMENTAL | Patients receive pembrolizumab IV and enfortumab vedotin IV on study. Patients undergo radical nephroureterectomy and receive pembrolizumab IV on study Patients also undergo MRU imaging and undergo blood, urine and tissue sample collection throughout the study. |
| Treatment (enfortumab vedotin, pembrolizumab) | EXPERIMENTAL | Patients receive enfortumab vedotin IV and pembrolizumab IV on study. Patients also undergo CT scan or MRI, and collection of blood throughout the trial. |
| Cohort 1: HR+/HER2- breast cancer | EXPERIMENTAL | Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. HR+/HER2- = Hormone receptor-positive/ human epidermal growth factor receptor 2-negative |
| Cohort 2: Triple negative breast cancer (TNBC) | EXPERIMENTAL | Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. |
| Cohort 3: Squamous non-small cell lung cancer | EXPERIMENTAL | Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. |
| Cohort 4: Non-squamous non-small cell lung cancer | EXPERIMENTAL | Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. |
| Cohort 5: Head and neck cancer | EXPERIMENTAL | Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. |
| Cohort 6: Gastric or GEJ or esophageal cancer | EXPERIMENTAL | Participants enrolled into Cohort 6 will be reallocated based on disease type and histology into Cohorts 7 or 8. GEJ= gastroesophageal junction |
| Cohort 7: Gastric and esophageal adenocarcinoma (EAC) including GEJ adenocarcinoma | EXPERIMENTAL | Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. |
| Cohort 8: Esophageal squamous cell carcinoma (ESCC) | EXPERIMENTAL | Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. |
| Cohort 9: Head and neck squamous cell carcinoma (HNSCC) | EXPERIMENTAL | Participants will receive enfortumab vedotin as an IV infusion on days 1 and 8 of each 21-day cycle. Pembrolizumab will be administered as an IV infusion on day 1 of each 21-day cycle. |
| Name | Type | Description |
|---|---|---|
| Enfortumab vedotin | DRUG | Enfortumab vedotin administered as an IV infusion on Days 1 and 8 of every 3-week cycle |
| Pembrolizumab | DRUG | IV infusion on Day 1 of every 3-week cycle |
| Cisplatin | DRUG | administered as IV infusion on Day 1 of each 3-week cycle |
| Carboplatin | DRUG | Dosed according to local guidelines and will be administered as IV infusion on Day 1 of each 3-week cycle |
| Gemcitabine | DRUG | IV infusion on Days 1 and 8 of every 3 week cycle |
| Radiation | RADIATION | The preference will be a four-week schedule, in which 55 Gy radiotherapy will be administered using intensity modulated radiation therapy (IMRT) |
| Chemoradiation | OTHER | by local protocol; by local protocol; Mitomycin C/fluoropyrimidines in the Netherlands) * No disease outside the bladder (e.g. involvement of ureter, prostatic urethra or (suspected) lymph node metastases) * No bilateral hydronephrosis * No multifocal CIS * Adequate bladder function: Post-micturition residual volume of \< 200 cc, International Prostate Symptom Score (IPSS) \< 15 points; revised urinary incontinence scale \< 8 points; no daily or continuous catheter use. |
| Cystectomy | PROCEDURE | Surgical removal of the bladder |
| Biopsy | PROCEDURE | Undergo tissue biopsy |
| Biospecimen Collection | PROCEDURE | Undergo blood and urine collection |
| MR Urography | PROCEDURE | Undergo MRU |
| Nephroureterectomy | PROCEDURE | Undergo nephroureterectomy |
| Computed Tomography | PROCEDURE | Undergo CT |
| Magnetic Resonance Imaging | PROCEDURE | Undergo MRI |
| Questionnaire Administration | OTHER | Ancillary studies |
Inclusion Criteria: * Histologically documented, unresectable locally advanced or metastatic urothelial carcinoma * Measurable disease by investigator assessment according to RECIST v1.1 * Participants with prior definitive radiation therapy must have measurable disease per RECIST v1.1 that is o...
Enfortumab Vedotin is an investigational antibody-drug conjugate being studied for multiple urothelial cancers, including muscle invasive bladder urothelial carcinoma, urothelial bladder cancer, renal pelvis and ureter urothelial carcinoma, bladder squamous cell carcinoma, and locally advanced or metastatic malignant solid tumors. It is also being evaluated in combination with pembrolizumab for various bladder cancer settings.
Enfortumab Vedotin is a monoclonal antibody (mab) that targets Nectin-4, a cell adhesion protein highly expressed on urothelial cancer cells. It delivers a microtubule-disrupting agent directly to tumor cells, leading to cell death. This targeted mechanism is being investigated across multiple clinical trials for bladder and urothelial cancers.
Enfortumab Vedotin is being developed by Merck & Company, Inc., traded on the New York Stock Exchange under the ticker MRK. The company is conducting clinical trials to evaluate the drug's safety and efficacy in various urothelial cancer indications, including combination studies with pembrolizumab.
Enfortumab Vedotin is currently in Phase 2 clinical development for several indications, including muscle invasive bladder urothelial carcinoma, urothelial bladder cancer, and renal pelvis and ureter urothelial carcinoma. It is also being studied in a Phase 3 trial for untreated locally advanced or metastatic urothelial cancer, though the overall development stage is Phase 2.
Enfortumab Vedotin is being evaluated in multiple trials, including NCT04223856 (Phase 3, active not recruiting, 886 participants) for urothelial cancer, NCT05756569 (Phase 2, recruiting) for bladder cancer of variant histology, NCT05775471 (Phase 2, recruiting) for high-risk upper tract urothelial cancer, and NCT07663747 (Phase 2, not yet recruiting) for muscle invasive bladder cancer.
Yes, Enfortumab Vedotin is also known as Enfortumab vedotin (EV). This alternative name is commonly used in clinical trial titles and medical literature. Researchers and clinicians may refer to the drug as EV when discussing combination regimens, such as EV plus pembrolizumab, in the context of urothelial cancer treatment.