DISITAMAB VEDOTIN for Urothelial carcinoma

Inclusion criteria

• {"criterion_text":"- Expected survival ≥12 weeks\n- Locally-advanced unresectable or metastatic (American Joint Commission on Cancer Stages TNM Stage IIIB–IV [Amin 2017]) UC with histopathological confirmation, including UC originating from the renal pelvis, ureters, bladder, or urethra. Mixed-cell type tumors are eligible as long as urothelial (transitional cell) carcinoma is the predominant cell type.\n- Prior therapy: a.Participantsmust have received only 1 or 2 lines of prior systemic therapy for LA/mUC, including 1 line of platinum-containing chemotherapy. i.Neoadjuvant or adjuvant systemic therapy, with progression within 12 months of completing final dose of therapy, is considered as one line of prior therapy. ii.Maintenance avelumab therapy delivered following first-line platinum therapy is not considered a separate line of therapy. iii.Prior therapy with PD-(L)1 inhibitors as (neo)adjuvant therapy, first-line maintenance therapy or as second-line treatment is allowed.\n- Radiographically documented disease progression during or after the most recent line of therapy for LA/mUC\n- At least one measurable lesion by investigator assessment based on RECIST version 1.1.\n- Participants must be willing and able to provide archived (formalin-fixed paraffin-embedded tumor tissue blocks (or alternatively freshly sectioned slides; see laboratory manual for details and Section 7.1.3). This must be obtained prior to study treatment initiation and will be sent to a sponsor-designated central laboratory for biomarker analysis. If archival tissue is not available, then a newly obtained baseline biopsy of an accessible tumor lesion is required within 28 days prior to the Cycle 1 Day 1. Biopsy must provide adequate tissue for HER2 testing.\n- HER2-expression status determined by the central laboratory to be IHC 1+, 2+ or 3+, on the provided tumor tissue sample of muscle-invasive or metastatic UC.\n- Participants must have an ECOG performance status of 0 or 1."}

Exclusion criteria

• {"criterion_text":"- Known hypersensitivity to disitamab vedotin or any of their components\n- Received antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc.) or participated in another clinical study within 2 weeks prior to the start of the study (defined as Cycle 1 Day 1 for Cohorts A and B)\n- Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia)\n- Prior MMAE-based ADCs (eg, enfortumab vedotin) or HER2-directed therapy\n- Major surgery that has not fully recovered within 4 weeks prior to dose administration\n- Peripheral sensory or motor neuropathy ≥ Grade 2 at baseline\n- Received live or live-attenuated vaccines within 4 weeks prior to study treatment initiation or plan on receiving such vaccines during the course of study treatment\n- Participants with acute, chronic or symptomatic infections, including: A. Ongoing symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. B. History of human immunodeficiency virus infection. C. History of hepatitis B virus (HBV) infection (defined as positive for HBV surface antigen) or known active hepatitis C virus (HCV) infection (defined as HCV RNA [qualitative] is detected).\n- Other serious, uncontrolled concomitant diseases that may affect protocol compliance or interpretation of outcomes, including active opportunistic infections or advanced (severe) infections, or uncontrolled diabetes."}

Primary endpoints

• {"endpoint_text":"- cORR (confirmed CR and confirmed PR) per RECIST v1.1 as assessed by BICR","definition_or_measurement_approach":"Per RECIST v1.1 as assessed by Blinded Independent Central Review (BICR)"}
• {"endpoint_text":"- cORR per RECIST v1.1 as assessed by BICR","definition_or_measurement_approach":"Per RECIST v1.1 as assessed by Blinded Independent Central Review (BICR)"}

Secondary endpoints

• {"endpoint_text":"- cORR per RECIST v1.1, as assessed by the investigator","definition_or_measurement_approach":"Per RECIST v1.1 as assessed by the investigator"}
• {"endpoint_text":"- Confirmed DOR per RECIST v1.1, as assessed by BICR ● Confirmed DOR per RECIST v1.1, as assessed by the investigator","definition_or_measurement_approach":"Duration of Response per RECIST v1.1 assessed by BICR and by investigator"}
• {"endpoint_text":"- PFS per RECIST v1.1, as assessed by BICR ● PFS per RECIST v1.1, as assessed by the investigator","definition_or_measurement_approach":"Progression-free survival per RECIST v1.1 assessed by BICR and by investigator"}
• {"endpoint_text":"- DCR (confirmed CR, confirmed PR, and stable disease) per RECIST v1.1, as assessed by BICR ● DCR per RECIST v1.1, as assessed by the investigator","definition_or_measurement_approach":"Disease control rate per RECIST v1.1 assessed by BICR and by investigator"}
• {"endpoint_text":"- OS","definition_or_measurement_approach":"Overall survival (time to death from any cause)"}
• {"endpoint_text":"- Type, incidence, relatedness, severity and seriousness of AEs ● Treatment discontinuations, dose reductions, or dose delays due to AEs ● Type, incidence and severity of laboratory abnormalities ● ECG abnormalities, including changes in QTc ● Effect on LVEF","definition_or_measurement_approach":"Safety and tolerability assessments including adverse events, lab abnormalities, ECG (QTc), and left ventricular ejection fraction (LVEF)"}
• {"endpoint_text":"- PK parameters of disitamab vedotin, free MMAE, and TAb","definition_or_measurement_approach":"Pharmacokinetic parameters for disitamab vedotin, unconjugated MMAE, and total antibody (TAb)"}
• {"endpoint_text":"- Incidence of ADA and NABs against disitamab vedotin","definition_or_measurement_approach":"Incidence of anti-drug antibodies (ADA) and neutralising antibodies (NABs)"}

France

Earliest CTIS Part Ii Submission Date

19-02-2024

Latest Decision Or Authorization Date

29-04-2024

Processing Time Days

70

Number Of Sites

5

Number Of Participants

4

Spain

Earliest CTIS Part Ii Submission Date

28-02-2024

Latest Decision Or Authorization Date

18-06-2025

Processing Time Days

475

Number Of Sites

7

Number Of Participants

4

Italy

Earliest CTIS Part Ii Submission Date

04-03-2024

Latest Decision Or Authorization Date

05-06-2025

Processing Time Days

458

Number Of Sites

6

Number Of Participants

4

Belgium

Earliest CTIS Part Ii Submission Date

13-03-2024

Latest Decision Or Authorization Date

15-05-2025

Processing Time Days

428

Number Of Sites

2

Number Of Participants

2

Primary sponsor

Full Name

Seagen Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Icon Clinical Research LLC

Responsibilities

CRO

Third parties

• {"country":"United States","full_name":"Advarra Inc.","duties_or_roles":"Site and Patient Portal","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"ePRO Tablets","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Frontage Laboratories Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"HER2 (CDx) Analysis – European sites","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"PK/ADA Analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Database (CRF)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"RTSM/IRT","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Cellcarta Naperville LLC","duties_or_roles":"PD-L1 Analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Cardiac Safety","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"Tissue DNA & RNA analysis and storage – global","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Ireland","full_name":"Accellacare Limited","duties_or_roles":"PK Day 8 blood draw","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Icon Clinical Research LLC","duties_or_roles":"CRO","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Stark Raving LLC","duties_or_roles":"Patient Recruitment Materials","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Ventana Medical Systems Inc.","duties_or_roles":"HER2 (CDx) Analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Imaging","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient Reimbursement","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"RNA/DNA sequencing","organisation_type":"Laboratory/Research/Testing facility"}