Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatments and Combinations in Patients With Urothelial Carcinoma (MORPHEUS-UC)

Summary

A Phase Ib/II, open-label, multicenter, randomized, umbrella study in participants with MIBC and in participants with locally advanced or metastatic Urothelial Carcinoma (UC) who have progressed during or following a platinum-containing regimen. The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, or modify the participant population (e.g., with regard to prior anti-cancer treatment or biomarker status). Participants in the mUC Cohort who experience loss of clinical benefit or unacceptable toxicity during Stage 1 may be eligible to continue treatment with a different treatment regimen for Stage 2.

Conditions

• Urothelial Carcinoma
• Bladder Cancer

Interventions

DRUG

Atezolizumab

For the control, + EV, + Nira, + Tira, and + SG arms, + RO7122290, Atezolizumab will be administered intravenously (IV) at a fixed dose of 1200 mg every 3 weeks (Q3W) on Day 1 of each 21-day cycle. For the Atezo + Hu5F9-G4 and + TCZ arms, Atezo will be administered IV at a fixed dose of 840 mg every 2 weeks (Q2W) on Days 1 and 15 of each 28-day cycle.

DRUG

Enfortumab Vedotin

Enfortumab vedotin will be administered at a dose of 1.25 mg/kg IV on Days 1 and 8 of each 21-day cycle.

DRUG

Niraparib

Niraparib will be administered at a dose of 200 mg once daily (QD) by mouth.

DRUG

Magrolimab (Hu5F9-G4)

Participants will receive an 1-mg/kg priming dose IV on Day 1 followed by three weekly IV doses of 30 mg/kg on Days 8, 15, and 22. During Cycle 2, participants will receive weekly IV doses of 30 mg/kg on Days 1, 8, 15, and 22. For all subsequent cycles, participants will receive 30 mg/kg on Days 1 and 15. Cycle = 28 days.

DRUG

Tiragolumab

Tiragolumab will be administered at a dose of 600 mg IV on Day 1 of each 21-day cycle.

DRUG

Sacituzumab Govitecan

Sacituzumab Govitecan will be administered at a dose of 10 mg/kg by IV on Day 1 and 8 of each 21-day cycle.

DRUG

Tocilizumab

Tocilizumab will be administered by IV infusion at a dose of 8 mg/kg every 4 weeks (Q4W) on Day 1 of each 28-day cycle.

DRUG

Cisplatin

Cisplatin will be administered at a dose of 70mg/m\^2 by IV on Day 1 of each cycle for Cycles 1-3 pre-surgery.

DRUG

Gemcitabine

Gemcitabine will be administered at a dose of 1000mg/m\^2 by IV on Days 1 and 8 of each cycle for Cycles 1-3 pre-surgery.

Sponsors & Collaborators

• Gilead Sciences, Inc., GlaxoSmithKline plc, Seattle Genetics and Astellas

  collaborator UNKNOWN

• Hoffmann-La Roche

  lead INDUSTRY

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-06-01

Primary Completion

2025-10-08

Completion

2025-12-22

FDA Drug

Yes

Countries

• United States
• France
• Greece
• South Korea
• Spain
• Taiwan
• United Kingdom

Study Locations