(UroToday.com) The 2023 European Society of Medical Oncology (ESMO) Annual Congress held in Madrid, Spain between October 20th and 24th, 2023 hosted a urothelial and other cancers abstract poster session for trials in progress. Dr. Shilpa Gupta presented the study framework for a global, multicentre, open-label, randomised phase II trial of tobemstomig with or without tiragolumab versus atezolizumab in patients with untreated metastatic urothelial cancer ineligible for platinum-based chemotherapy.
Platinum-based chemotherapy remains a standard of care treatment option for the majority of patients with previously untreated metastatic urothelial carcinoma. Treatment options for patients ineligible for any platinum-based therapy remain limited/poorly defined and include PD-1 or PD-L1 immune checkpoint inhibitors or other regimens such as single-agent chemotherapy.
Since many patients treated with immune checkpoint inhibitors do not experience durable treatment responses, additional options are needed to mitigate resistance and improve patient outcomes. Combinations targeting novel checkpoints (e.g., LAG3, TIGIT) are attractive as they address distinct resistance mechanisms that could expand the number of patients who respond to immune checkpoint inhibitors, while also potentially offering a tolerable risk-benefit profile.
Tobemstomig is a novel bispecific antibody with monovalent binding to PD-1 and LAG3, a cell surface immune checkpoint which acts as a co-inhibitory receptor to suppress T cells activation and cytokines secretion ensuring a state of immune homeostasis. Tiragolumab is an antibody that binds TIGIT, an immune checkpoint inhibiting lymphocyte T cells via several mechanisms. In this trial, the efficacy and safety of atezolizumab (Arm A, control) versus tobemstomig (Arm B) or tobemstomig + tiragolumab (Arm C) will be evaluated as 1st line therapy in platinum-ineligible patients with metastatic urothelial carcinoma.
The target study sample size is 240 patients meeting the following eligibility criteria:
- Age ≥18 years
- Locally advanced or metastatic urothelial carcinoma
- Measurable disease
- Available tumor sample
- No prior checkpoint inhibitor therapy or 1st line systemic therapy
- Platinum ineligible with ≥1 of the following:
- ECOG PS 0 with GFR 15-30 mL/min/1.73 m2
- ECOG PS 1-2 with GFR 15-45 mL/min/1.73 m2
- ECOG PS 0-2 with Grade ≥2 neuropathy
- Chemo not deemed appropriate per investigator
Patients will be recruited from 83 sites across 15 countries and randomized 1:1:1 to receive:
- Atezolizumab 1,200 mg IV
- Tobemstomig 600 mg IV every 3 weeks
- Tobemstomig 600 mg IV + tiragolumab 600 mg IV every 3 weeks
Treatment will continue until clinical benefit is lost or unacceptable toxicity development. Randomization 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).
The primary endpoint will be an investigator-assessed confirmed objective response rate (Tobemstomig and tobemstomig + tiragolumab compared to atezolizumab control arm). Secondary endpoints include progression-free survival, overall survival, duration of response, duration of complete response, and safety outcomes.
Presented by: Dr. Shilpa Gupta, MD, Associate Professor, Director of the Genitourinary Medical Oncology at Taussig Cancer Institute and Co-Leader of the Genitourinary Oncology Program at Cleveland Clinic, Cleveland, OH
Written by: Rashid K. Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 European Society of Medical Oncology (ESMO) Annual Meeting, Madrid, Spain, Fri, Oct 20 – Tues, Oct 24, 2023.