Neoplasms

All Conditions

Rare Diseases

Carcinoma

Carcinoma, Transitional Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Transitional Cell Carcinoma

Participants will receive an intravenously (IV) administered dose once weekly for the first 3 weeks of every 4-week cycle (i.e., on days 1, 8, and 15)

enfortumab vedotin (EV)

Medical Director

The primary purpose of this expanded access program is to evaluate safety and tolerability of enfortumab vedotin (EV) in participants in the United States with locally advanced or metastatic urothelial carcinoma (UC) who have exhausted standard of care therapies and are not eligible to participate in an ongoing EV clinical study. This program will also evaluate the efficacy of EV.

This treatment protocol is being conducted while a phase 3 enfortumab vedotin (EV) study is ongoing for participants with previously treated locally advanced or metastatic urothelial carcinoma (UC).

This is an expanded access program to provide EV to participants with locally advanced or metastatic UC who have previously been treated with a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor, and a platinum containing regimen and for whom, in the judgment of the investigator, there is no available standard of care therapy. The participants must not be eligible for an ongoing EV clinical study. Participants who have previously participated in any EV studies or studies that included EV as one of the treatment options are not eligible, even if the participants was not given or assigned EV. To request enrollment, the investigator or designee will submit the candidate participant's relevant medical history and other records in order to support the participant's protocol eligibility.

Safety of EV will be assessed through evaluation of adverse events (AEs), serious adverse events (SAEs), Eastern Cooperative Oncology Group (ECOG) performance status, laboratory measurements, vital signs and physical examinations.

Participants will be provided with study medication until FDA approval and commercial availability of enfortumab vedotin (EV) or termination by the sponsor.

An Expanded Access Treatment Protocol of Enfortumab Vedotin in Subjects With Locally Advanced or Metastatic Urothelial Carcinoma

A Multicenter, Open-label, Expanded Access Treatment Protocol of Enfortumab Vedotin in Subjects With Locally Advanced or Metastatic Urothelial Carcinoma (EV-901)

Seagen Inc.

Astellas Pharma Global Development, Inc.

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Urinary Bladder Neoplasms

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Sacituzumab govitecan

Avelumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immunoconjugates

Immunologic Factors

Participants will receive avelumab intravenous infusion at a dose of 800 milligrams (mg) once every 2 weeks (Q2W) until unacceptable toxicity, withdraw consent or initiation of a new treatment.

Participants will receive sacituzumab govitecan intravenous infusion at dose of 10 milligrams per kilogram (mg/kg) of body weight once a week (Q1W) on Day 1 and 8 of 21-day treatment cycles, in combination with avelumab 800 mg Q2W, until unacceptable toxicity, withdraw consent or initiation of a new treatment.

Sacituzumab Govitecan

Participants will receive M6223 (anti-T cell-immuno-receptor with Ig and ITM domains \[anti-TIGIT\]) intravenous infusion at dose of 1600 mg Q2W in combination with avelumab 800 mg Q2W, until unacceptable toxicity, withdraw consent or initiation of a new treatment.

M6223

Participants will receive NKTR-255 intravenous infusion at a dose of 3 micrograms per kilogram body weight (mcg/kg) once every 4 weeks (Q4W) in combination with avelumab 800 mg Q2W, until unacceptable toxicity, withdraw consent or initiation of a new treatment.

NKTR-255

US Medical Information

Communication Center

Saqib Abbasi

Jean Hoffman Censits

Jaswinder J Singh

Petros Grivas

Sunil Rangarajan

Christos Kyriakopoulos

Ganessan Kichenadasse

Cameron McLaren

Shirley Wong

Andrew J Weickhardt

Annabel Smith

Wei Chua

James Lynam

Andrew G Hill

Alexander Guminski

Alison Y Zhang

Megan Crumbaker

Wesley Teurfs

Wim Demey

Nieves Martinez Chanza

Sylvie Rottey

Philip Debruyne

Frederic Forget

Pierre Freres

Anna K Seitz

Marco Iafolla

Catherine Sperlich

Normand Blais

Christina M Canil

Dorthe Yakymenko

Andreas Carus

Remy Delva

Guilhem Roubaud

Elodie Coquan

Christophe Tournigand

Eric Voog

Aude Flechon

Jean Laurent Deville

Nadine Houede

Olivier Huillard

Nicolas Isambert

Brigitte Laguerre

Frederic Rolland

Louis Marie Dourthe

Philippe Barthelemy

Herbert Sperling

Viktor Gruenwald

Severine Banek

Georgios Gakis

Katrin Schlack

Rausch Steffen

Marinos Tsiatas

Flora Zagouri

Aristotelis Bamias

Loukas Kontovinis

Francesco Massari

Lorenzo Antonuzzo

Ugo De Giorgi

Valentina Guadalupi

Andrea Necchi

Michele Caruso

Rosa Tambaro

Fabio Calabro

Marco Maruzzo

Luca Galli

Francesco Carrozza

Linda Cerbone

Giampaolo Tortora

Evaristo Maiello

Sergio Bracarda

Hyo Jin Lee

Ho Kyung Seo

SE HYUN KIM

Jae Lyun Lee

Se Hoon Park

Miso Kim

Sang Joon Shin

In Ho Kim

Marta Gonzalez Cordero

Oscar Reig Torras

Jose Pablo Maroto Rey

Alejo Rodriguez-Vida

Begona Perez Valderrama

Maria Jose Mendez Vidal

Federico Vazquez Mazon

Sergio Vazquez Estevez

Jose Angel Arranz Arija

Mariona Figols Gorina

Isabel Chirivella Gonzalez

Yu Li Su

Shu-Pin Huang

Hsi-Chin Wu

Chien-Liang Li

Medical Responsible

The purpose of this study is to assess the safety and efficacy of avelumab in combination with other anti-tumor agents as a maintenance treatment in participants with bladder cancer.

A Study of the Safety and Efficacy of Various Combinations of Avelumab as Therapy in Locally Advanced or Metastatic Urothelial Carcinoma (JAVELIN Bladder Medley)

A Phase II, Multicenter, Randomized, Open Label, Parallel-Arm, Umbrella Study of Avelumab (MSB0010718C) in Combination With Other AntiTumor Agents as a Maintenance Treatment in Participants With Locally Advanced or Metastatic Urothelial Carcinoma Whose Disease Did Not Progress With First Line Platinum-Containing Chemotherapy (JAVELIN Bladder Medley)

We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21

Merck KGaA, Darmstadt, Germany; Gilead Sciences; Nektar Therapeutics

EMD Serono Research & Development Institute, Inc.

Atezolizumab

Cisplatin

Immune Checkpoint Inhibitors

Part A: Part A is conducted in patients who are cisplatin-ineligible and have had no prior systemic treatment for locally advanced or metastatic disease.

Patients will receive rogaratinib plus atezolizumab combination treatment.

Part A:Rogaratinib will be administered orally until disease progression, unacceptable toxicity or consent withdrawal. The starting dose of 800 mg b.i.d. will be confirmed using a dose selection design.

Rogaratinib (BAY1163877)

Part A: A fixed dose of 1200 mg atezolizumab will be administered through intravenous (i.v.) infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity or consent withdrawal.

FORT-2 is designed to evaluate safety, efficacy, RP2D and PK of rogaratinib in combination with atezolizumab in patients with untreated FGFR-positive urothelial carcinoma. The study originally comprised two separate parts: Phase 1b (Part A) and Phase 2 (Part B). The study parts differ in design, objectives, and treatment.

The primary objectives of this Phase 1b study (Part A) are to determine the safety, tolerability, RP2D and pharmacokinetics of rogaratinib in combination with atezolizumab in these patients.

The primary objective of the Part B is to compare progression-free survival (PFS) according to RECIST v1.1 of rogaratinib in combination with atezolizumab over placebo in combination with atezolizumab in untreated patients with FGFR-positive locally advanced or metastatic urothelial carcinoma.

Of note, patients who participate in Part A are not allowed to participate in Part B.

Part B will be initiated once the data from Part A supports continuation of the study, even if this occurs prior to primary completion of Part A. The sponsor may decide not to continue the study as a whole after completion of Part A if the data do not support further development.

Part B of the study will no longer be conducted.

Phase 1b/2 Study of Rogaratinib (BAY1163877) in Combination With Atezolizumab in Urothelial Carcinoma

An International, Multicenter, Phase 1b/2 Study of Rogaratinib (BAY1163877) in Combination With Atezolizumab as First-line Treatment in Cisplatin-ineligible Patients With FGFR-positive Locally Advanced or Metastatic Urothelial Carcinoma

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

A DLT is defined as any of the hematological, non-hematological or other TEAEs occurring during Cycle 1 and regarded by the investigators and/or sponsor to be related to rogaratinib or atezolizumab. The CTCAE v 4.03 will be used to assess toxicities / adverse events.

Part A:Objective response rate (ORR) is defined as the percentage of patients with complete response (CR) or partial response (PR). Patients for whom best overall tumor response is not CR or PR, as well as patients without any post-baseline tumor assessment will be considered non-responders.

For all patients, the best overall tumor response will be determined locally by investigators using the RECIST criteria (v1.1).

Bayer

Japanese Patients With Locally Advanced or Metastatic Urothelial Carcinoma who were treated with avelumab as first-line maintenance therapy

The purpose of this clinical trial is to learn about the current treatment patterns, safety, and effects of the study medicine (Avelumab) for the treatment of urothelial carcinoma.

This study is seeking Japanese participants who:

* have urothelial cancer that has spread
* are treated with Avelumab for maintenance

We will study the experiences of people receiving avelumab. This helps us learn the current treatment patterns, safety, and effects of avelumab. Participants will take part in this study up to 10 months. During this time, they will have no study visits.

A Study to Learn About the Study Medicine (Avelumab) in Japanese Patients With Urothelial Carcinoma That Has Spread

Retrospective, Multicenter, Observational Study to Evaluate Current Treatment Patterns and Outcomes in Japanese Patients With Locally Advanced or Metastatic Urothelial Carcinoma Treated With First-line Avelumab Maintenance

We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21

TTF is defined as the following:

TTF, defined as the time from start of avelumab maintenance therapy to the date of end of treatment due to any cause including death. If there is no record of the end of treatment, it be discontinued on the last visit date during the study period.

rwPFS is defined as the following: The time from start of avelumab maintenance therapy to date of first disease progression (as clinically assessed by local investigator based on radiology, laboratory evidence, pathology, or other assessments) or death due to any cause, whichever occurred first. If there were no clinical records of death or disease progression, they will be censored at the date of initiation of the next line of therapy for the patients undertaking 2 or more lines of therapy (subsequent therapy after avelumab maintenance therapy) based on the record, or at their last visit date during the study period for the patients undertaking only 1 line of therapy (only avelumab maintenance therapy) based on the record.

Objective Response is defined as the following:

Complete or partial response as the best adjudication result (CR \> PR \> SD \> PD) in a method that complies with Response Evaluation Criteria in Solid Tumors (RECIST) version. 1.1 tumor assessment as closely as possible in clinical practice by investigator's judgment.

rwPFS-c is defined as the following: The time from start of first-line Chemotherapy to date of first disease progression (as clinically assessed by local investigator based on radiology, laboratory evidence, pathology, or other assessments) or death due to any cause during avelumab treatment, whichever occurred first. If there were no clinical records of death or disease progression, they will be censored at the date of initiation of the next line of therapy for the patients undertaking 2 or more lines of therapy (subsequent therapy after avelumab maintenance therapy) based on the record, or at their last visit date during the study period for the patients undertaking only 1 line of therapy (only avelumab maintenance therapy) based on the record.

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
An Expanded Access Treatment Protocol of Enfortumab Vedotin in Subjects With Locally Advanced or Metastatic Urothelial Carcinoma	NCT04136808	Locally Advance...	enfortumab vedo...	18 Years -	Astellas Pharma Inc
An Expanded Access Treatment Protocol of Enfortumab Vedotin in Subjects With Locally Advanced or Metastatic Urothelial Carcinoma	NCT04136808	Locally Advance...	enfortumab vedo...	18 Years -	Astellas Pharma Inc
A Study of the Safety and Efficacy of Various Combinations of Avelumab as Therapy in Locally Advanced or Metastatic Urothelial Carcinoma (JAVELIN Bladder Medley)	NCT05327530	Locally Advance...	Avelumab Sacituzumab Gov... M6223 NKTR-255	18 Years -	EMD Serono
Phase 1b/2 Study of Rogaratinib (BAY1163877) in Combination With Atezolizumab in Urothelial Carcinoma	NCT03473756	Urothelial Carc...	Rogaratinib (BA... Atezolizumab	18 Years -	Bayer
A Study to Learn About the Study Medicine (Avelumab) in Japanese Patients With Urothelial Carcinoma That Has Spread	NCT05431777	Urothelial Carc...	Avelumab	0 Years -	Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Spots Global Cancer Trial Database for locally advanced or metastatic urothelial carcinoma