227TiP - A phase II, open label, randomized, non-comparative cohorts study of adjuvant atezolizumab or atezolizumab plus tiragolumab in solid tumors with resectable disease with intermediate-high risk of recurrence and high tumor mutational burden (TMB-H) or microsatellite instability (MSI-H)

Background

Solid tumor treatment has changed in last years with the introduction of PD-1/PD- L1 checkpoint inhibitors, improving long-term survival. The drugs that inhibit the activity of TIGIT (T-cell immunoreceptor with Ig and ITIM domains) like Tiragolumab (TG) may relieve an important source of tumor-associated immune suppression and enhance the activity of inhibitors of PD-L1, as atezolizumab (AT) is. With the recent FDA approvals of immunotherapy in patients harboring TMB-H and MSI-H tumors in the metastatic field, the recent adjuvant immunotherapy data and the early efficacy data of anti-PD-(L)1 plus anti-TIGIT combination, it is of considerable interest to study these strategies in a high-risk biomarker selected population after standard (neo)adjuvant therapy.

Trial design

A phase II, multicenter, open-label, randomized study will assess efficacy and safety of two non-comparative cohorts, one using AT and the other one AT plus TG in patients with solid tumors and high TMB (≥13 mut/MB) or high MSI in resectable stages after standard systemic treatment and/or surgery and at intermediate-high risk of recurrence. The primary endpoint will be the Disease-Free Survival (DFS) rate at 24 months. The study will consist of two phases: a pre-screening phase to assess biomarker eligibility and patients will use standard treatment according to investigators choice and the study treatment phase. All patients will receive AT or AT in combination with TG. The first cohort will include 20 patients treated with AT 1680 mg every four weeks (Q4W) for 12 cycles, administered intravenously on Day 1 of each 28-day cycle. The second cohort will include 20 patients treated with AT 1680 mg Q4W plus TG 840 mg Q4W for 12 cycles, administered intravenously on Day 1 of each 28-day cycle. No crossover will be allowed between cohorts. The total duration of study participation for patients is expected to be around 12 months, with follow-up of 60 months for disease recurrence.

Clinical trial identification

EudraCT 2022-003708-33.

Editorial acknowledgement

Legal entity responsible for the study

Roche.

Funding

Roche.

Disclosure

S. Pons, E. Garrido, R. Galan Servan: Financial Interests, Full or part-time Employment: Roche. All other authors have declared no conflicts of interest.