LBA-5 Phase Ib study of the anti-TIGIT antibody tiragolumab in combination with atezolizumab in patients with metastatic esophageal cancer

Abstract

TIGIT (T-cell Immunoreceptor with Ig and ITIM domains) is a novel inhibitory immune checkpoint present on activated T cells and NK cells in multiple cancers, including esophageal cancer, and is often co-expressed with PD-1 on tumor infiltrating immune cells. Tiragolumab is a fully human IgG1/kappa monoclonal antibody that binds TIGIT to prevent its interaction with its ligand PVR (CD155). A phase Ib dose-escalation and dose-expansion study (GO30103, NCT02794571) showed that tiragolumab combined with atezolizumab was tolerable, and activity was seen in an expansion cohort of patients with PD-L1-positive non-small cell lung cancer (Bendell et al., 2020). We now report preliminary safety and anti-tumor activity of tiragolumab + atezolizumab in patients with metastatic esophageal cancer not previously treated with cancer immunotherapy. Patients enrolled in this phase Ib expansion cohort had metastatic esophageal cancer that had progressed on available therapies, had ECOG PS 0–1 and had not been treated previously with cancer immunotherapy. Patients were enrolled from the USA, EU, and Asia. PD-L1 expression was determined by central immunohistochemistry review. Patients received tiragolumab 400 mg or 600 mg IV every 3 weeks (Q3W) + atezolizumab 1200 mg IV Q3W until disease progression, intolerable toxicity, or patient/investigator decision to withdraw. The safety, tolerability, and preliminary anti-tumor activity of tiragolumab + atezolizumab in patients with metastatic esophageal cancer not previously treated with cancer immunotherapy were evaluated at a data cut-off date of 8 April 2021. Twenty-one patients with metastatic esophageal cancers were treated (histopathological subtypes: squamous [13 patients], adenocarcinoma [7 patients] and neuroendocrine [1 patient]). Median age was 62 years; 5 patients (23.8%) had ECOG PS 0 and 16 patients (76.2%) had ECOG PS 1; 15 patients (71.4%) had received ≥2 prior therapies; 7 patients (33.3%) were from Asia and 14 patients (66.7%) were from US/EU. Treatment-related AEs (TRAEs), as assessed by investigators, occurred in 14 patients (66.7%), with a Grade 3 TRAE seen in 1 patient. Immune-mediated AEs (imAEs) occurred in 12 patients (57.1%). No Grade 4 or 5 TRAEs or imAEs were observed. The most common AEs reported (in ≥15% of patients) were malignant neoplasm progression (28.6%), anemia (23.8%), decreased appetite, cough, aspartate aminotransferase increase, amylase increase (all 19.0%). Of 18 evaluable patients with at least one tumor assessment, there were 5 partial responses (objective response rate of 27.8%). The disease control rate was 50%, with 1 patient still in the study at 2+ years. Tiragolumab combined with atezolizumab was well-tolerated with an acceptable safety profile, and showed preliminary antitumor activity in heavily pretreated patients with metastatic esophageal cancers not previously treated with cancer immunotherapy.