A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatments and Combinations in Patients with Urothelial Carcinoma Morpheus-UC

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

4 Jun 2019 → 22 Dec 2025

Decision date (initial)

2024-07-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

External identifiers

EU CT number

2024-511316-25-00

EudraCT number

2017-004634-28

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Others, Pharmacokinetic

Metastatic urothelial carcinoma cohort (mUC) cohort: To evaluate the efficacy of immunotherapy-based treatment combinations during Stage 1 based on Objective response rate MIBC cohorts: To evaluate the efficacy of treatment in patients treated perioperatively for MIBC based on pathologic complete response

Secondary objectives 4

1. mUC cohort: To evaluate the efficacy of immunotherapy-based treatment combinations during Stage 1 based on progression-free survival, overall survival after randomization, overall survival rate at specific time points (e.g., 12 months), duration of response, Disease control
2. To evaluate the safety of immunotherapy-based treatment combinations during Stage 1 and Stage 2
3. MIBC cohorts: To evaluate the efficacy of treatment in patients treated perioperatively for MIBC based on landmark recurrence-free survival, event-free survival, and overall survival at specific timepoints
4. MIBC cohorts: To evaluate the safety of treatment in patients treated perioperatively for MIBC

Conditions and MedDRA coding

Urothelial carcinoma (UC)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Stage 1: Availability of a representative tumor specimen that is suitable for determination of Programmed death-ligand 1 (PD-L1) and/or additional biomarker status by means of central testing
2. Stage 1: Disease progression during or following treatment with no more than one platinum containing regimen for inoperable, locally advanced or metastatic UC or disease recurrence
3. Stage 1 and Stage 2 Measurable disease according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST) v1.1
4. Stage 1 and Stage 2 Negative HIV test at screening
5. For the Muscle Invasive Bladder Cancer Cohorts (MIBC) Availability of a TURBT specimen that is suitable for determination of PD-L1 and additional biomarker status by means of central testing
6. For the Muscle Invasive Bladder Cancer Cohorts (MIBC) N0 or M0 disease assessed by CT or magnetic resonance imaging (MRI) scan (within 4 weeks of study treatment initiation)

Exclusion criteria 6

1. For mUC cohort: Stage 1 Prior treatment with a T-cell co-stimulating therapy or an immune checkpoint inhibitor, or investigational therapy within 28 days before C1D1, or any approved anti-cancer therapy within 3 weeks before study
2. For mUC cohort: Stage 1 and Stage 2 Prior systemic immunostimulatory treatments within 4 weeks or 5 half-lives of the drug before study, or with systemic immunosuppressants within 2 weeks before study, or need such during study
3. For mUC cohort: Stage 1 and Stage 2 History of leptomeningeal disease, autoimmune disease, idiopathic pulmonary fibrosis (IPF), organizing pneumonia drug-induced pneumonitis, or idiopathic pneumonitis, or active pneumonitis at screening
4. For mUC cohort: Stage 1 and Stage 2 Active tuberculosis (TB)
5. For MIBC Cohorts Received a live, attenuated vaccine within 4 weeks before study, or needing such during atezolizumab treatment or within 5 months after the last dose
6. For MIBC Cohorts Active or history of autoimmune disease or immune deficiency

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1. Objective response rate (mUC Cohort)
2. 2. Pathological complete response (MIBC Cohorts)

Secondary endpoints 10

1. 1. Progression-free survival
2. 2. Overall survival after randomization
3. 3. Overall survival rate at specific time points
4. 4. Duration of response
5. 5. Disease control
6. 6. Incidence, nature, and severity of adverse events and laboratory abnormalities, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0
7. 7. Change from baseline in vital signs
8. 8. Change from baseline in targeted clinical laboratory test results MIBC Cohorts
9. 9. Landmark recurrence-free survival, event-free survival and overall survival MIBC Cohorts
10. 10. Incidence, nature, and severity of adverse events and laboratory abnormalities, with severity determined according to NCI CTCAE v4.0

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 15

Locations

3 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 21 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications