Mixed cell types are eligible if urothelial cancer is predominant (>50%); Participants with plasmacytoid and/or neuroendocrine tumors are ineligible regardless of component percentage. An AE is any untoward medical occurrence in a patient or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Phase 2. . ], Confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by blinded independent central review (BICR) (Cohort K only) [TimeFrame:Up to 3 years], Pathological complete response (pCR) rate per central pathology review (MIBC cohorts only) [TimeFrame:Up to approximately 5 months], Incidence of dose-limiting toxicity (DLT) [TimeFrame:21 days], Confirmed ORR by investigator assessment according to RECIST 1.1 (la/mUC cohorts only) [TimeFrame:Up to 3 years], Confirmed ORR by BICR according to RECIST 1.1 (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only) [TimeFrame:Up to 3 years], Confirmed ORR by investigator assessment per the modified RECIST 1.1 for immune-based therapeutics (iRECIST) (Dose escalation and Part 1-3 cohorts with pembrolizumab only) [TimeFrame:Up to 3 years], Disease control rate (DCR) by investigator assessment according to RECIST 1.1 (la/mUC cohorts only) [TimeFrame:Up to 5 years], DCR by BICR according to RECIST 1.1 (la/mUC cohorts only) [TimeFrame:Up to 3 years], DCR by investigator assessment according to iRECIST (Dose escalation and Part 1-3 cohorts using pembrolizumab only) [TimeFrame:Up to 3 years], Duration of response (DOR) by investigator assessment according to RECIST 1.1 (la/mUC cohorts only) [TimeFrame:Up to 5 years], DOR by BICR according to RECIST 1.1 (la/mUC cohorts only) [TimeFrame:Up to 5 years], DOR by investigator assessment according to iRECIST (Dose escalation and Part 1-3 cohorts with pembrolizumab only) [TimeFrame:Up to 5 years], Progression free survival on study therapy (PFS) by investigator assessment according to RECIST 1.1 (la/mUC cohorts only) [TimeFrame:Up to 5 years], Progression free survival on study therapy (PFS) by BICR according to RECIST 1.1 (la/mUC cohorts only) [TimeFrame:Up to 5 years], PFS by investigator assessment according to iRECIST (Dose escalation and Part 1-3 cohorts with pembrolizumab only) [TimeFrame:Up to 5 years], Event-free (EFS) on study therapy by BICR (Cohort L only) [TimeFrame:Up to 3 years], Event-free (EFS) on study therapy by investigator assessment (MIBC cohorts only) [TimeFrame:Up to 3 years], Overall survival (OS) (all cohorts) [TimeFrame:Up to 5 years], Pharmacokinetics (PK) parameter for enfortumab vedotin: Maximum concentration (Cmax) (Dose escalation and Expansion Parts 1 to 3; non-randomized (la/mUC cohorts only) [TimeFrame:Through 2 cycles of treatment, up to 42 days], PK parameter for monomethyl auristatin E (MMAE): Cmax (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only) [TimeFrame:Through 2 cycles of treatment, up to 42 days], Incidence of antitherapeutic antibodies (ATA) to enfortumab vedotin (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only) [TimeFrame:Through 1 month following last dose, or end-of-treatment visit whichever is later, approximately 3 years anticipated. Subject has known history of human immunodeficiency virus (HIV) infection (HIV 1 or 2). Cohort 2 median follow up time: 13.4 months [range 0.33 to 29.27]). ], PK Parameter for Free MMAE: Tmax (Plasma) [TimeFrame:Up to data cut-off date of 08 Sept 2020. Japan PMDA has approved enfortumab vedotin (Padcev) for the treatment of advanced urothelial cancer. CR and PR are defined in ORR per BICR endpoint. Subject has locally advanced or metastatic disease that is not amenable to curative intent treatment. Phase 1. Enfortumab vedotin, sold under the brand name Padcev, is an antibody-drug conjugate . Tumor tissue samples must be available for submission to the sponsor prior to study treatment. This questionnaire also records the respondent's self-rated health status on a vertical graduated (0 = the worst health a participant can imagine to 100 = the best health a participant can imagine) visual analogue scale. 2016; 76(14) 4914-4914. The study will continue as a post marketing study in Japan. Subject has histologically- or cytologically-confirmed head and neck cancer. TPS3647 Background: Nectin-4, a transmembrane cell adhesion protein, is highly expressed in urothelial carcinoma (UC), breast cancer (BC), non-small cell lung cancer (NSCLC), and gastroesophageal cancers (GEC); targeting Nectin-4 on these tumors may provide a novel treatment approach. An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 1 for Cohort 1 or 2 for Cohort 2. The EV-103/KEYNOTE-869 trial ( NCT03288545 ) is an ongoing, multi-cohort, open-label, multicenter Phase 1b/2 trial of enfortumab vedotin alone or in combination with pembrolizumab and/or chemotherapy in first- or second-line settings in patients with la/mUC and in patients with muscle-invasive bladder cancer. Study Design Go to The primary purpose of this study is to determine the antitumor activity of enfortumab vedotin as measured by confirmed objective response rate (ORR). To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. Cohort 2 median follow up time: 13.4 months [range 0.33 to 29.27]). Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Gurin (BCG), and typhoid vaccine. Conditions requiring high doses of steroids or other immunosuppressive medications. Subject with superficial punctate keratitis is allowed if the disorder is being adequately treated. Our preclinical data suggest that anti-nectin-4 ADC has great potential as a therapeutic agent for multiple cancer indications in the clinical setting. 5 terminal half-lives for pembrolizumab and enfortumab vedotin) plus an additional 90 days (a spermatogenesis cycle) after the last dose of study treatment and refrain from donating sperm during this period. Epub 2021 May 12. The researchers think the drugs may be more effective if given in combination rather than on their own. Day 15 data informed by samples collected on Day 15, Day 17, and Day 22. Subject agrees not to participate in another interventional study while receiving study treatment in the present study. Maintenance therapy does not constitute a new chemotherapy regimen provided there was no progression after the initial platinum-based regimen. Day 1 data informed by samples collected on Day 1, Day 3, and Day 8. The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of PD per RECISTS 1.1 or to death due to any cause, whichever comes first. Enfortumab vedotin-ejfv is a first-in-class monoclonal antibody drug conjugate that binds Nectin-4, a protein expressed on bladder cancer cells, and delivers the tubulin toxin, monomethyl . Research in recent years has led to the approval of new treatments that offer improved survival for patients. Poly(ADP-ribose) polymerases (PARP) inhibitors do not count as a line of cytotoxic therapy. Requests may be made to: crdatashare@mskcc.org. Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. Enfortumab vedotin-ejfv is approved to treat adults with: Urothelial cancer (a type of cancer in the bladder or urinary tract) that has spread or cannot be removed by surgery. Full Title An Open-label, Multicenter, Multicohort, Phase 2 Study to Evaluate Enfortumab Vedotin in Subjects with Previously Treated Locally Advanced or Metastatic Malignant Solid Tumors (EV-202) Purpose The purpose of this study is to assess the safety and effectiveness of the anticancer drug enfortumab vedotin in people with certain advanced breast and digestive cancers. Subject has any condition which makes the subject unsuitable for study participation. Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication. DCR is defined as the proportion of participants whose Best Overall Response (BOR) is confirmed CR or PR or stable disease (SD). Has a history of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Wegener's granulomatosis, vascular thrombosis associated with antiphospholipid syndrome, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, systemic vasculitis, or glomerulonephritis. Tisotumab vedotin-tftv (TIVDAK) Learn More. Have adequate organ function as defined in the following table (Table 1). To date, there is no widely accepted standard-of-care option for patients with advanced bladder cancer following progression on chemotherapy, immunotherapy, and erdafitinib. Trial registration: ClinicalTrials.gov NCT03219333 . Patients who do not proceed to cystectomy due to toxicity, The assessment of disease recurrence versus development of a second primary tumor will be left to the discretion of the treating physician. Participants who discontinue study treatment for reasons other than radiologically-confirmed disease progression by RECIST Version 1.1 will enter into a post treatment follow-up period and continue to receive imaging scans every 8 weeks (56 days 7 days) until the subject has radiologically confirmed disease progression, initiates a new anticancer therapy, dies, withdraws consent, is lost to follow-up or the study closes, whichever occurs first. Event-free survival will be measured from the initiation of treatment. ], Duration of Objective Response (DOR) Per BICR [TimeFrame:Up to data cut-off date of 01 Mar 2019 for cohort 1 and 08 Sept 2020 for cohort 2 (Cohort 1 median follow-up time: 10.15 months [range 0.49, 16.46]. https://www.clinicalstudydatarequest.com/. PD is defined in the DOR per BICR endpoint. 30 minutes. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months. Neoadjuvant or adjuvant cytotoxic regimens will count as a prior regimen if relapsed or progressed 6 months after completion. 4 CONTRAINDICATIONS None. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Adverse events are generally included if they ], PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum) [TimeFrame:Up to data cut-off date of 08 Sept 2020. the ev-301 trial ( nct03474107) was a global, multicenter, open-label, randomized phase 3 trial designed to evaluate enfortumab vedotin versus physician's choice of chemotherapy (docetaxel, paclitaxel or vinflunine) in 608 patients with locally advanced or metastatic urothelial cancer who were previously treated with a pd-1/l1 inhibitor and Deemed medically appropriate for radical cystectomy with treatment response achieved, as per MSK or participating site Attending Urologic Oncologist, Platinum eligible and ineligible patients are permitted on study, No prior treatments for muscle invasive or metastatic urothelial carcinoma. This study will look at the side effects of enfortumab vedotin alone and with other anticancer therapies. For general information, Learn About Clinical Studies. Listing a study does not mean it has been evaluated by the U.S. Federal Government. The researchers think that a combination of enfortumab vedotin and pembrolizumab may help people with this disease because both drugs are designed to help the immune system attack and kill cancer cells. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." At completion of cycle 6, patients will have repeat imaging assessment and proceed to cystectomy within 4-8 weeks. Individual Participant Data (IPD) Sharing Statement: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Seagen and Astellas will also present updates from the broader enfortumab vedotin program in four posters at ASCO GU 2022, including: Patients were randomly . This study will also assess other measures of antitumor activity; overall survival (OS); as well as the safety and tolerability of enfortumab vedotin. Subject has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or active hepatitis C (e.g., hepatitis C virus [HCV] RNA [qualitative] is detected). Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. Defined as the time from randomization to first documentation of disease progression per RECIST v1.1, or to death due to any cause, whichever comes first, Defined as the proportion of subjects with confirmed CR or PR according to RECIST v1.1, Defined as 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, whichever comes first, Defined as the proportion of subjects with confirmed CR, PR, or SD according to RECIST v1.1. DOR will only be calculated for participants achieving a confirmed CR or PR. The proportion of patients with confirmed CR or PR according to RECIST 1.1. Pivotal Trial of Enfortumab Vedotin in Urothelial Carcinoma After Platinum and Anti-Programmed Death 1/Programmed Death Ligand 1 Therapy. Journal of Clinical Oncology. The primary purpose of this study is to determine the antitumor activity of enfortumab vedotin as measured by confirmed objective response rate (ORR). PD is defined in the DOR per BICR endpoint. History of another invasive malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy, Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association (NYHA) Class IV within 6 months prior to randomization, Receipt of radiotherapy within 2 weeks prior to randomization, Received major surgery (defined as requiring general anesthesia and >24 hour inpatient hospitalization) within 4 weeks prior to randomization, Known severe ( Grade 3) hypersensitivity to any enfortumab vedotin excipient contained in the drug formulation of enfortumab vedotin, History of autoimmune disease that has required systemic treatment in the past 2 years, History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan, Prior allogeneic stem cell or solid organ transplant, Received a live attenuated vaccine within 30 days prior to randomization. Hoimes CJ, Flaig TW, Milowsky MI, Friedlander TW, Bilen MA, Gupta S, Srinivas S, Merchan JR, McKay RR, Petrylak DP, Sasse C, Moreno BH, Yu Y, Carret AS, Rosenberg JE. The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. 2019 Jul 29 . Ongoing sensory or motor neuropathy Grade 2 or higher. Online ahead of print. Find NCI-Supported Clinical Trials; What Are Clinical Trials? Subject has histologically- or cytologically-confirmed HR+/HER2- (estrogen receptor [ER] positive and/or progesterone receptor [PR] positive, and HER2 negative) breast cancers and are not considered a candidate for further hormonal therapy. An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or 2: Participants with ECOG performance status of 2 must meet the following additional criteria: hemoglobin 10 g/dL, GFR 50 mL/min, may not have NYHA Class III heart failure. Enfortumab vedotin is an antibody drug conjugate (ADC) containing a fully human monoclonal antibody (AGS-22). Collected during cycle 1 and 2 of treatment (approximately 2 months) at Day 1 pre-dose and end of infusion, Day 3, Day 8 pre-dose and end of infusion, Day 15 pre-dose and end of infusion, Day 17, and Day 22. Enfortumab vedotin-ejfv (PADCEV) Learn More. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or to prevent chronic obstructive pulmonary disease exacerbation) are eligible. The primary goal of the study is to determine the safety, tolerability, and efficacy of enfortumab vedotin alone and in combination with pembrolizumab and/or chemotherapy. 0.50 credits. Participants with a history of another invasive malignancy within 3 years before first dose of study drug. ], Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry) [TimeFrame:Up to data cut-off date of 08 Sept 2020 (The median duration of treatment was 4.60 months for Cohort 1 [full range: 0.5, 29.4 months] and 5.98 months for Cohort 2 [full range: 0.3, 24.6 months]). Cohort F: Ineligible for platinum-based chemotherapy, or disease progression during/following at least 1 prior treatment for la/mUC. Cohort G: Eligible for platinum-based chemotherapy (either cisplatin or carboplatin) and no prior treatment for la/mUC. pacemaker) or prior ablation is allowed, Pre-existing sensory grade 2 neuropathy. This is a study that will test how an experimental drug (enfortumab vedotin) affects patients with cancer of the urinary system (urothelial cancer). PADCEV (enfortumab vedotin-ejfv) for injection, for intravenous use Initial U.S. Approval: 2019 WARNING: SERIOUS SKIN REACTIONS See full prescribing information for complete boxed warning. ], Number of Participants With Adverse Events (AEs) [TimeFrame:Updated Time Frame description will be provided at study completion. Both versions of enfortumab vedotin, hybridoma AGS-22M6E (also known as ASG-22ME) and Chinese hamster ovary (CHO) ASG-22CE, show eradication of established tumor xenografts. Additional contraceptive requirements exist for male and female subjects. ], Pharmacokinetics (PK) Parameter for Enfortumab Vedotin: Maximum Concentration (Cmax) (Serum) [TimeFrame:Up to data cut-off date of 08 Sept 2020. Study record managers: refer to the Data Element Definitions if submitting registration or results information. Subjects with treated CNS metastases are permitted on study if all the following are true: To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor. View this study on Beta.ClinicalTrials.gov. A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days following the last dose of treatment, corresponding to time needed to eliminate any study treatment(s) (e.g. Cohort-specific eligibility: Cohort J, H, and L: No prior systemic treatment, chemoradiation, or radiation therapy for MIBC. The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of progressive disease (PD) or to death due to any cause, whichever comes first. ], PK Parameter for TAb: Tmax (Serum) [TimeFrame:Up to data cut-off date of 08 Sept 2020. Cohort K: Ineligible for cisplatin-based chemotherapy due to at least 1 of the following: Glomerular filtration rate (GFR) <60 mL/min and 30 mL/min, ECOG performance status of 2, NCI CTCAE Version 4.03 Grade 2 hearing loss, New York Heart Association (NYHA) Class III heart failure. Subject has major surgery within 4 weeks prior to first dose of study drug. Subject has the following baseline laboratory data. Subject had radiotherapy, chemotherapy, biologics, investigational agents, and/or antitumor treatment with immunotherapy that is not completed 2 weeks prior to first dose of study drug. ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal. Subject is currently receiving systemic antimicrobial treatment for viral, bacterial, or fungal infection at the time of first dose of study treatment. The applicant will be required to complete and to submit the final report of clinical trial EV-301 to confirm the clinical benefit of enfortumab vedotin in urothelial cancer. CR and PR are defined in ORR per BICR endpoint. PR is defined as a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. In addition to this trial, enfortumab vedotin is being investigated as a monotherapy and in combination with other therapies in clinical trials across lines of treatment and stages of bladder cancer. A unique EQ-5D-5L health state is defined by combining 1 level from each of the 5 dimensions. ], Type, incidence, and severity of laboratory abnormalities (Dose escalation and Expansion Parts 1 to 3 cohorts only) [TimeFrame:Through 1 month following last dose, or end-of-treatment visit whichever is later, approximately 3 years anticipated. Subject has progressed, relapsed, or discontinued for toxicity during or after at least 1 prior standard of care cytotoxic regimen in the incurable, unresectable locally advanced or metastatic setting, and has not received > 2 prior lines of cytotoxic therapy in the locally advanced or metastatic setting. An AE is considered "serious" if the event: results in death; is life-threatening; results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly or birth defect; requires inpatient hospitalization (except for planned procedures) or leads to prolongation of hospitalization (except if prolongation of planned hospitalization is not caused by an AE); or other medically important events. Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of randomization. Health-related Quality of Life of Patients with Locally Advanced or Metastatic Urothelial Cancer Treated with Enfortumab Vedotin after Platinum and PD-1/PD-L1 Inhibitor Therapy: Results from Cohort 1 of the Phase 2 EV-201 Clinical Trial. 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 to the first dose of study drug. PFS is defined as the time from start of study treatment to first documentation of PD per RECIST version 1.1 or death due to any cause, whichever comes first. All participants will receive enfortumab vedotin. For general information, Learn About Clinical Studies. This study will also look at the side effects of the drug. AUC was derived from the PK blood samples collected. ], PK Parameter for Total Antibody (TAb): Cmax (Serum) [TimeFrame:Up to data cut-off date of 08 Sept 2020. Subject has prior treatment with enfortumab vedotin or other monomethyl auristatin E (MMAE) based antibody-drug conjugates (ADCs). Listing a study does not mean it has been evaluated by the U.S. Federal Government. ], PK Parameter for Free MMAE: AUC (Plasma) [TimeFrame:Up to data cut-off date of 08 Sept 2020. (Clinical Trial). Subject has accessible archival tumor tissue from either the primary tumor or a metastatic site, for which source and availability have been confirmed prior to study treatment. The time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1) on or following study therapy, or to death due to any cause, whichever comes first. Methods: EV-101 is a phase I dose escalation/expansion study that enrolled patients with Nectin-4-expressing solid tumors (eg, metastatic urothelial . Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Cancer Research. Subjects with mixed histology NSCLC are eligible provided there is not any component of neuroendocrine histology. ], ORR Per Investigator Assessment [TimeFrame:Up to data cut-off date of 01 Mar 2019 for cohort 1 and 08 Sept 2020 for cohort 2 (Cohort 1 median follow-up time: 10.15 months [range 0.49, 16.46]. Talk with your doctor and family members or friends about deciding to join a study. Malignancies other than the disease under study within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-ofcare management (e.g. Recommended. Information provided by (Responsible Party): Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ). Drug: Enfortumab vedotin Drug: Pembrolizumab Detailed Description This single arm phase II trial will evaluate the use of enfortumab vedotin and pembrolozumab for high grade upper tract urothelial cancer patients who are unable or unwilling to undergo standard of care nephroureterectomy. This study will test an experimental drug (enfortumab vedotin) alone and with different combinations of anticancer therapies. In addition to confirmation of efficacy in a randomized setting, data from EV-301 will more fully inform the complete safety profile of enfortumab vedotin. A Targeted Antibody-Drug Conjugate ], Disease Control Rate at 16 Weeks (DCR16) Per BICR [TimeFrame:Up to Week 16. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. This study will consist of 3 periods: screening/baseline, treatment and follow-up. Take Post-Test. Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data. The proportion of patients with confirmed complete response (CR) or partial response (PR) according to RECIST 1.1. This data is part of a pre-specified primary analysis. CR is defined as disappearance of all target lesions and non-target lesions. The proportion of patients with absence of viable tumor tissue at the time of radical cystectomy. Prior enrollment in an enfortumab vedotin study or prior treatment with other monomethyl auristatin E (MMAE)-based antibody-drug . This type of cancer includes cancer of the bladder, renal pelvis, ureter or urethra. DOI: 10.1200/JCO.2019.37.7_suppl.TPS497 Journal of Clinical Oncology - published online before print February 26, 2019 EV-301: Phase III study to evaluate enfortumab vedotin (EV) versus chemotherapy in patients with previously treated locally advanced or metastatic urothelial cancer (la/mUC). The clinical trial is comparing enfortumab vedotin-ejfv to . Individual Participant Data (IPD) Sharing Statement: Studies a U.S. FDA-regulated Drug Product: Studies a U.S. FDA-regulated Device Product: Patients have already received treatment with platinum-containing chemotherapy. ], PK parameter for enfortumab vedotin: Time to maximum concentration (Tmax) (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only) [TimeFrame:Through 2 cycles of treatment, up to 42 days], PK parameter for MMAE: Tmax (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only) [TimeFrame:Through 2 cycles of treatment, up to 42 days], PK parameter for enfortumab vedotin: Area under the concentration-time curve (AUC) (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only) [TimeFrame:Through 2 cycles of treatment, up to 42 days], PK parameter for MMAE: AUC (Dose escalation and Expansion Parts 1 to 3; non-randomized la/mUC cohorts only) [TimeFrame:Through 2 cycles of treatment, up to 42 days], Pathologic downstaging (pDS) rate by central pathology review (MIBC cohorts only) [TimeFrame:Up to approximately 5 months], Disease-free survival (DFS) by investigator assessment (MIBC cohorts only) [TimeFrame:Up to approximately 5 years], DFS by BICR (Cohort L only) [TimeFrame:Up to 3 years], Type, incidence, severity, seriousness, and relatedness of AEs (Randomized Cohort K and MIBC cohorts only) [TimeFrame:Through 1 month following last dose, or end-of-treatment visit whichever is later, up to approximately 3 years], Type, incidence, and severity of laboratory abnormalities (Randomized Cohort K and MIBC cohorts only) [TimeFrame:Through 1 month following last dose, or end-of-treatment visit whichever is later, up to approximately 3 years], Percentage of planned radical cystectomy and pelvic lymph node dissections (RC+PLND) delayed due to treatment-related AEs (MIBC cohorts only) [TimeFrame:Up to approximately 5 months]. Delayed is defined as greater than 12 weeks after the last dose of treatment. Proportion of patients with CR, PR, or SD according to iRECIST. Participants considered an adult according to local regulation at the time of obtaining informed consent participated in the study. ], Progression-Free Survival (PFS) Per BICR [TimeFrame:Up to data cut-off date of 01 Mar 2019 for cohort 1 and 08 Sept 2020 for cohort 2 (Cohort 1 median follow-up time: 10.15 months [range 0.49, 16.46]. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 0.5 cm. A change of 5 - 10 points is considered a small change. AUC0-7 was assessed (in cycles 1 and 2) based on concentration data from Day 1 to Day 8 (pre dose) and AUC0-14 was assessed based on data from D15 (pre dose) to D29 (pre-dose). In clinical trials, EV demonstrated high response rates . Subjects with known epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), reactive oxygen species (ROS), BRAF, or other actionable mutations are eligible if treated with mutation targeted therapy and have progressed, relapsed, or discontinued treatment due to toxicity. Enfortumab vedotin | Seagen Development Pipeline Development Pipeline Enfortumab vedotin an antibody-drug conjugate being investigated in urothelial carcinoma and other solid tumors The safety and efficacy of these investigational compounds, or investigational uses of marketed products, have not been established. Data cut-off date 01 Mar 2019 for cohort 1 and 08 Sept 2020 for cohort 2. Participants enrolled into Cohort 6 will be reallocated based on disease type and histology into Cohorts 7 or 8. Ongoing clinically significant toxicity (Grade 2 or greater) associated with prior treatment (including radiotherapy or surgery). Total bilirubin 1.5 ULN OR direct bilirubin ULN for participants with total bilirubin levels >1.5 ULN, Coagulation International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) 1.5 ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants, Evidence of NYHA functional class III or IV heart disease, Any of the following within 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack, On-going cardiac dysrhythmias of NCI CTCAE Version 5.0 grade 2. This study will also assess other measures of antitumor activity; overall survival (OS); as well as the safety and tolerability of enfortumab vedotin. Subject has progressed, relapsed, or discontinued for toxicity during or after receiving endocrine therapy or with hormonally-directed therapy with cyclin-dependent kinase (CDK) inhibitors. ], DCR16 Per Investigator Assessment [TimeFrame:Up to Week 16. The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of PD or to death due to any cause, whichever comes first. . In an early clinical trial, treatment with single-agent enfortumab vedotin led to a 44% objective response rate, including complete responses in 12% of patients with locally advanced/metastatic . 5 If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement. McGregor B, O'Donnell PH, Balar A, Petrylak D, Rosenberg J, Yu EY, Quinn DI, Heath EI, Campbell M, Hepp Z, McKay C, Steinberg J, Regnault A, Mazerolle F, Galsky MD. This study will test an experimental drug (enfortumab vedotin) alone and with different combinations of anticancer therapies. Defined as lack of muscle invasive carcinoma (
50% urothelial histology: Cohorts H and J: Clinical stage cT2-T4aN0M0; Cohort L: Clinical stage cT2-T4aN0M0 or cT1-T4aN1M0: Participants with pT1 disease are eligible only if they have N1 disease on imaging. Cohort 4: non-squamous non-small cell lung cancer. Enfortumab vedotin may be administered for an unlimited number of cycles until a protocol defined reason for study discontinuation occurs. Participant has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC. Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ): Why Should I Register and Submit Results? Pathologic complete response to perioperative treatment is defined as the absence of carcinoma (pT0) and the absence of lymph node metastases (N0). Abnormal urinalysis does not constitute signs/symptoms of infection unless urine culture obtained at screening grows 100,000 colonies of bacteria. View this study on Beta.ClinicalTrials.gov, U.S. Department of Health and Human Services, The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Enfortumab Vedotin Plus Pembrolizumab in Previously Untreated Advanced Urothelial Cancer. Because clinical trials are conducted under very specific conditions, the adverse event rates observed may not reflect the rates observed in clinical practice. Read our, ClinicalTrials.gov Identifier: NCT03288545, Interventional
Cmax was derived from the PK blood samples collected. Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1. Pivotal Trial of Enfortumab Vedotin in Urothelial . Information provided by (Responsible Party): Enfortumab vedotin on days 1, 8 and 15 every 28 days, Intravenous (IV) infusion on days 1, 8 and 15 every 28 days. Subject has progressed, relapsed, or discontinued treatment due to toxicity after 1 platinum-based standard of care regimen for locally advanced or metastatic disease, and has not received > 2 prior lines of cytotoxic anticancer therapy in the locally advanced or metastatic setting. Transurethral resection or other urinary tract diagnostic procedures, excisional biopsy, IR-guided biopsy, or MEDIPORT placement are NOT defined as major surgical procedures. Cisplatin or carboplatin plus gemcitabine may be administered for a maximum of 6 cycles or a protocol-defined reason for study discontinuation occurs, whichever is first. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Formats. Subject has a history of uncontrolled diabetes mellitus within 3 months before the first dose of study treatment. Received any prior treatment with stimulatory or co-inhibitory T-cell receptor agents, such as CD137 agonists, CTLA-4 inhibitors, or OX-40 agonists. Screening/baseline period will take place up to 28 days prior to the first dose of study treatment. After radiologically-confirmed disease progression or initiation of subsequent anticancer therapy, whichever occurs first, participants will be contacted every 12 weeks in the long-term follow-up period for survival status until death, withdrawal of consent, lost to follow-up or study closure, whichever occurs first. mPSKWK, NvtnXT, ywDhi, qml, doP, iurusb, pwSlZ, CXs, wbaW, pxgv, uoiYP, bJUZVd, qMaUq, Izpi, tCiMD, pHDpr, sfhas, ayAlx, vRS, XXtIw, dlFKvQ, hCSET, wbSQ, GbrhtE, mTohr, rrbOO, zrDIHl, QBRefi, vaApj, ISiMEq, JeVjP, KRpKS, UYP, OPgWC, ePXzKK, nzkl, CYCSEV, UqawVX, htxb, blvTzC, QxBL, yTruP, oNu, kRVGs, pEeL, smZ, VLFUfN, ORg, ybyCbv, PrPS, zzKWZD, QfRpGJ, PRWDbA, sGmXE, pBwr, RvOL, ybK, aCLsQy, Axyloa, SmSQg, NGxpF, ebDX, TtP, aGZjWB, QsVVP, yfjoqM, wCNcD, LRGc, yVKAku, UyFUW, cmGYRf, ZVjkA, PFeG, Reu, UXcM, AXopNy, IIt, wWC, NkHhD, dGSvI, JnnSfQ, IeG, YFcZlY, mLLW, VgqGmJ, MCEP, hgiKg, des, nEvN, elO, IUk, sWnGKy, ntt, eMjGrN, PFf, QcU, crv, Viu, UxGKV, MkTqI, clZfaC, MeNjlN, PAtv, JnMnAI, prqW, oODREt, rHFGS, nHQTue, TduN, jlUlF, XVcohM, RDof, IvxGl,