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

• ClinicalTrials.gov Identifier: NCT05645692
• Recruitment Status: Recruiting
• First Posted: December 9, 2022
• Last Update Posted: May 14, 2024
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: November 28, 2022
• First Posted Date: December 9, 2022
• Last Update Posted Date: May 14, 2024
• Actual Study Start Date: April 13, 2023
• Estimated Primary Completion Date: December 30, 2026 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: December 7, 2022): Confirmed Objective Response Rate (ORR) [ Time Frame: Up to approximately 30 months ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 6, 2023)

• Progression-Free Survival (PFS) [ Time Frame: Up to approximately 30 months ]
• Overall Survival (OS) [ Time Frame: Up to approximately 30 months ]
• Duration of Response (DOR) [ Time Frame: Up to approximately 30 months ]
• PFS [ Time Frame: 6 months and 12 months ]
• OS [ Time Frame: 6 months, 12 months, and 18 months ]
• Disease Control Rate (DCR) [ Time Frame: Up to 12 weeks ]
• Time to Confirmed Deterioration (TTCD) [ Time Frame: Baseline up to 3 weeks ]
• Change from Baseline in European Organisation for Research and Cancer Treatment Item Library 187 (EORTC IL 187) Scores [ Time Frame: Up to approximately 30 months ]
• Maximum Concentration (Cmax) of Tobemstomig [ Time Frame: Up to approximately 30 months ]
• Time of Maximum Concentration (Tmax) of Tobemstomig [ Time Frame: Up to approximately 30 months ]
• Clearance (CL) of Tobemstomig [ Time Frame: Up to approximately 30 months ]
• Volume of Distribution at Steady State (Vss) of Tobemstomig [ Time Frame: Up to approximately 30 months ]
• Area Under the Curve (AUC) of Tobemstomig [ Time Frame: Up to approximately 30 months ]
• Half-Life (T1/2) of Tobemstomig [ Time Frame: Up to approximately 30 months ]
• Maximum serum concentration (Cmax) of tiragolumab [ Time Frame: Up to approximately 30 months ]
• Minimum serum concentration (Cmin) of tiragolumab [ Time Frame: Up to approximately 30 months ]
• Cmax of atezolizumab [ Time Frame: Up to approximately 30 months ]
• Cmin of atezolizumab [ Time Frame: Up to approximately 30 months ]
• Incidence of Anti-Drug Antibodies (ADAs) [ Time Frame: Up to approximately 30 months ]

Original Secondary Outcome Measures (submitted: December 7, 2022)

• Progression-Free Survival (PFS) [ Time Frame: Up to approximately 30 months ]
• Overall Survival (OS) [ Time Frame: Up to approximately 30 months ]
• Duration of Response (DOR) [ Time Frame: Up to approximately 30 months ]
• PFS [ Time Frame: 6 months and 12 months ]
• OS [ Time Frame: 6 months, 12 months, and 18 months ]
• Disease Control Rate (DCR) [ Time Frame: Up to 12 weeks ]
• Time to Confirmed Deterioration (TTCD) [ Time Frame: Baseline up to 3 weeks ]
• Change from Baseline in European Organisation for Research and Cancer Treatment Item Library 187 (EORTC IL 187) Scores [ Time Frame: Up to approximately 30 months ]
• Maximum Concentration (Cmax) of RO7247669 [ Time Frame: Up to approximately 30 months ]
• Time of Maximum Concentration (Tmax) of RO7247669 [ Time Frame: Up to approximately 30 months ]
• Clearance (CL) of RO7247669 [ Time Frame: Up to approximately 30 months ]
• Volume of Distribution at Steady State (Vss) of RO7247669 [ Time Frame: Up to approximately 30 months ]
• Area Under the Curve (AUC) of RO7247669 [ Time Frame: Up to approximately 30 months ]
• Half-Life (T1/2) of RO7247669 [ Time Frame: Up to approximately 30 months ]
• Maximum serum concentration (Cmax) of tiragolumab [ Time Frame: Up to approximately 30 months ]
• Minimum serum concentration (Cmin) of tiragolumab [ Time Frame: Up to approximately 30 months ]
• Cmax of atezolizumab [ Time Frame: Up to approximately 30 months ]
• Cmin of atezolizumab [ Time Frame: Up to approximately 30 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: A Phase II, Randomized, Multicenter, Open-Label, Controlled Study of Tobemstomig Alone or in Combination With Tiragolumab Versus Atezolizumab in Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer Who Are Ineligible for Platinum-Containing Chemotherapy
• Brief Summary: This study will evaluate the efficacy, safety, and pharmacokinetics of tobemstomig alone or in combination with tiragolumab compared with atezolizumab in participants with previously untreated, locally advanced or metastatic urothelial cancer (mUC) who are ineligible to receive a platinum containing chemotherapy.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Urothelial Cancer

Intervention

• Drug: Atezolizumab
  Participants will receive 1200 mg IV atezolizumab Q3W.
• Drug: Tobemstomig
  Participants will receive 600 mg IV tobemstomig Q3W.
  Other Name: RO7247669
• Drug: Tiragolumab
  Participants will receive 600 mg IV tiragolumab Q3W.

Study Arms

• Active Comparator: Arm A
  Participants will receive intravenous (IV) atezolizumab every 3 weeks (Q3W).
  Intervention: Drug: Atezolizumab
• Experimental: Arm B
  Participants will receive IV tobemstomig Q3W.
  Intervention: Drug: Tobemstomig
• Experimental: Arm C
  Participants will receive IV tobemstomig + IV tiragolumab Q3W.
  Interventions:

  • Drug: Tobemstomig
  • Drug: Tiragolumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 7, 2022): 240
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 30, 2026
• Estimated Primary Completion Date: December 30, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
• Histologically or cytologically documented locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium. Participants 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. Participants with other variant histologies or pure variant histologies are not eligible for inclusion in this study
• Ineligible ("unfit") to receive platinum-based chemotherapy
• No prior chemotherapy for inoperable locally advanced or metastatic or recurrent urothelial carcinoma (UC)
• Measurable disease; at least one measurable lesion as defined by response evaluation criteria in solid tumors, version 1.1 (RECIST v1.1)
• Availability of a representative leftover tumor specimen that is suitable for determination of PD-L1 status as assessed by a central laboratory
• Adequate hematologic and end organ function
• Negative for hepatitis B and hepatitis C virus (HCV)
• Adequate cardiovascular function

Exclusion Criteria:

• Pregnancy or breastfeeding
• GFR <15 mL/min/1.73 m2
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
• History of leptomeningeal disease
• Uncontrolled tumor-related pain
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
• Uncontrolled or symptomatic hypercalcemia
• 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 Epstein-Barr virus (EBV)
• Significant cardiovascular/cerebrovascular disease within 3 months prior to initiation of study treatment
• Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
• History of another primary malignancy other than urothelial carcinoma within 2 years prior to initiation of study treatment, with the exception of malignancies with a negligible risk of metastasis or death
• Severe infection within 4 weeks prior to initiation of study treatment
• Treatment with therapeutic oral or intravenous antibiotics within 2 weeks prior to initiation of study treatment. Participants receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease [COPD] exacerbation), or who are receiving oral antibiotics to treat a urinary tract infection are eligible for the study
• Prior allogeneic stem cell or solid organ transplantation
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during 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
• Current treatment with anti-viral therapy for HBV
• Treatment with any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment
• Treatment with investigational therapy within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-TIGIT and anti-LAG3 therapeutic antibodies or pathways targeting agents
• Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives prior to initiation of study treatment
• Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Reference Study ID Number: BO44157 https://forpatients.roche.com/; 888-662-6728; global-roche-genentech-trials@gene.com

• Listed Location Countries: Australia, Brazil, China, Denmark, France, Germany, Greece, Italy, Korea, Republic of, Mexico, Poland, Spain, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT05645692
• Other Study ID Numbers: BO44157
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-LaRoche

• PRS Account: Hoffmann-La Roche
• Verification Date: May 2024