2409TiP - A global, multicentre, open-label, randomised phase II trial of tobemstomig (tobe) with or without tiragolumab (tira) vs atezolizumab (atezo) in patients (pts) with untreated metastatic urothelial cancer (mUC) ineligible for platinum-based chemotherapy (chemo)

Background

Platinum-based chemo is the standard of care for the majority of pts with previously untreated mUC. Treatment options for pts ineligible for any platinum are not well defined and include PD-1 or PD-L1 immune checkpoint inhibitors (CPIs) or other regimens such as single-agent chemo, depending on clinical considerations. Because many pts treated with CPIs do not experience durable clinical benefit, additional treatments are needed to mitigate resistance and improve pt outcomes. Combinations targeting novel checkpoints (e.g., LAG3, TIGIT) are attractive as they address distinct resistance mechanisms that could expand the number of pts who respond to CPIs, while also potentially offering a tolerable benefit-risk profile. Tobe is a novel bispecific antibody with monovalent binding to PD-1 and LAG3, and tira is an antibody that binds TIGIT. In this trial, efficacy and safety of atezo (Arm A, control) vs tobe (Arm B) or tobe + tira (Arm C) will be evaluated as first-line (1L) therapy in platinum-ineligible pts with mUC.

Trial design

Approximately 240 pts aged ≥18 y with locally advanced or metastatic UC, measurable disease and available tumour sample will be enrolled across 15 countries and 83 sites. Pts must have no prior CPIs or 1L systemic therapy. Pts must be platinum ineligible based on one of the following criteria: (1) ECOG PS 0 with GFR 15-30 mL/min/1.73 m²; (2) ECOG PS 1-2 with GFR 15-45 mL/min/1.73 m²; (3) ECOG PS 0-2 with Grade ≥2 neuropathy or (4) chemo not deemed appropriate per investigator. Pts will be randomised 1:1:1 to receive atezo 1200 mg IV, tobe 600 mg IV or tobe 600 mg IV + tira 600 mg IV Q3W until loss of clinical benefit or unacceptable toxicity. Randomisation will be stratified by PD-L1 expression per VENTANA SP263 (investigational) (positive [tumour area positivity, TAP≥5% vs negative [TAP<5%]), baseline liver metastases (yes vs no; 15% cap), and ECOG PS (0 vs 1 or 2). This study will evaluate the effect of tobe and tobe + tira on investigator-assessed confirmed ORR (primary endpoint) relative to atezo. Secondary endpoints include PFS, OS, DOR, DCR and safety.

Clinical trial identification

NCT05645692.

Editorial acknowledgement

Medical writing assistance for this abstract was provided by Michael Williams, PhD, of Health Interactions, Inc. and funded by F. Hoffmann-La Roche Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

S. Gupta: Financial Interests, Personal, Advisory Board: Seattle Genetics, BMS, Pfizer, Bayer, Merck, Gilead, Loxo Oncology, Guardant, Foundation one; Financial Interests, Personal, Other, Speaker's Bureau: Janssen; Financial Interests, Personal, Other, Consultant: EMD Sorono; Financial Interests, Personal, Invited Speaker: Gilead; Financial Interests, Personal, Stocks/Shares: BioNTech, Moderna; Financial Interests, Personal, Steering Committee Member: BMS, Merck, Seattle Genetics, Acrivon; Financial Interests, Institutional, Local PI: EMD Sorono, Gilead, Roche, QED, Exelixis, Moderna, Pfizer. O. Alhalabi: Financial Interests, Personal, Advisory Board: Seagen, Silverback therapeutics, Cardinal health; Financial Interests, Personal, Invited Speaker: Curio Science; Financial Interests, Local PI: Ikena Oncology, Arcus Biosciences; Financial Interests, Institutional, Local PI: AstraZeneca; Non-Financial Interests, Principal Investigator: Genentech. A. Bamias: Financial Interests, Personal, Invited Speaker: Ipsen, Debiopharm; Financial Interests, Personal, Advisory Board: BMS, MSD, AstraZeneca; Financial Interests, Steering Committee Member: Roche; Financial Interests, Institutional, Coordinating PI: Roche, BMS, MSD; Financial Interests, Institutional, Funding: AstraZeneca, Pfizer; Non-Financial Interests, Leadership Role: Hellenic GU Cancer Group. J. Bellmunt: Financial Interests, Personal, Advisory Board, Joined the Global adboard this year: Pfizer; Financial Interests, Personal, Advisory Board, Regular GU adboard for bladder cancer: AstraZeneca; Financial Interests, Personal, Invited Speaker, Lectures in the setting of National meetings: Merck; Financial Interests, Personal, Advisory Board, Bladder adboard: Merck; Financial Interests, Personal, Advisory Board, For the adjuvant study CM 247: BMS; Financial Interests, Personal, Invited Speaker, For ESMO Asia Symp 2020 : MSD; Financial Interests, Personal, Stocks/Shares, Holdings: Bicycle; Financial Interests, Personal, Royalties, Role as Section Editor for Bladder: UpToDate; Financial Interests, Institutional, Coordinating PI, Pi of INDUCOMAIN Study (Avelumab first line in unfit patients) Though APRO Association: MSD; Financial Interests, Institutional, Coordinating PI, Pi of Prostate Study (Avelumab + Carboplatin) Though APRO Association: Pfizer; Non-Financial Interests, Other, Steering committee member of IMvigor 011: Genentech; Non-Financial Interests, Member: ASCO. 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