A Study Evaluating Different Immunotherapies (LAG-3 and PD-1 With or Without TIGIT, Compared to PD-L1 Alone) in Participants With Untreated Locally Advanced Metastatic Urothelial Cancer

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

13 Jan 2023 → ongoing

Decision date (initial)

2024-05-30

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

2023-504027-78-00

EudraCT number

2022-002265-15

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

1. To evaluate the safety of tobemstomig alone and in combination with tiragolumab, compared to atezolizumab

Conditions and MedDRA coding

Previously Untreated Locally Advanced or Metastatic Urothelial Cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
2. 2. Histologically or cytologically documented locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium. Patients with squamous, sarcomatoid, micropapillary, and glandular variant histologies are eligible for inclusion in the study, provided that a urothelial component is present in the tumor specimen. Patients with other variant histologies or pure variant histologies are not eligible for inclusion in the study
3. 3. Considered to be ineligible ("unfit") to receive platinum-based chemotherapy defined by one of the following criteria: • ECOG Performance Status of 0 with baseline GFR ≥ 15 mL/min/1.73 m2 and ≤ 30 mL/min/1.73 m2 • ECOG Performance Status of 1 or 2 with baseline GFR ≥ 15 mL/min/1.73 m2 and ≤ 45 mL/min/1.73 m2 • ECOG Performance Status of 0-2 with Grade ≥ 2 neuropathy • Patients for whom chemotherapy is not deemed appropriate
4. 4. No prior chemotherapy for inoperable locally advanced or metastatic or recurrent urothelial carcinoma (UC)
5. 5. Measurable disease; at least one measurable lesion as defined by response evaluation criteria in solid tumors, version 1.1 (RECIST v1.1)
6. 6. Availability of a representative leftover tumor specimen that meet the criteria outlined prior to study enrollment, and that is suitable for determination of programmed death-ligand 1 (PD-L1) status, and for stratification as assessed by a central laboratory

Exclusion criteria 6

1. 1. Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of atezolizumab, 4 months after the final dose of tobemstomig, or 90 days after the final dose of tiragolumab
2. 2. Glomerular filtration rate (GFR) < 15 mL/min/1.73 m2 as calculated through use of the chronic kidney disease epidemiology collaboration (CKD-EPI) equation or receiving dialysis
3. 3. Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
4. 4. History of leptomeningeal disease
5. 5. Uncontrolled tumor-related pain. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures and uncontrolled or symptomatic hypercalcemia
6. 6. Active or history of autoimmune disease or immune deficiency. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. Active tuberculosis (TB) or acute or chronic active Epstein-Barr virus (EBV)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Incidence and severity of adverse events, with severity determined according to national cancer institute common terminology criteria for adverse events, version 5.0 (NCI CTCAE v5), with the exception of Cytokine Release Syndrome (CRS) event severity which will be determined according to the American Society for Transplantation and Cellular Therapy (ASTCT)

Investigational products

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

Test 2

Comparator 1

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 5

Locations

7 EU/EEA countries · 29 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

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

Documents 57 files

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

Application history

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