According to results from a phase 3 trial, tiragolumab, a novel checkpoint inhibitor of TIGIT, plus atezolizumab, an anti-PD-L1 inhibitor, and chemotherapy showed statistically significant and clinically meaningful improvement in progression-free survival (PFS) and overall survival (OS) among patients with esophageal squamous cell carcinoma, when compared with placebo plus chemotherapy.

These results were first presented by Chih-Hung Hsu, MD, National Taiwan University Hospital, Taipei, Taiwan, at the 2024 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium on Thursday, January 18, 2024 in San Francisco, California.

In the SKYSCRAPER-08 trial 461 patients with locally advanced, unresectable recurrent, or metastatic esophageal squamous cell carcinoma were enrolled. Patients were randomized on a 1-to-1 basis to receive either 600mg tiragolumab plus 1200mg atezolizumab and paclitaxel and cisplatin chemotherapy (combination arm; n = 229), or placebo and chemotherapy (placebo arm; n = 232), followed by either tiragolumab and atezolizumab maintenance or placebo maintenance. The primary end points of this study were independently reviewed PFS and OS. Secondary end points included investigator assessed PFS, objective response rate, duration or response, and safety.

With a minimum follow-up of 6.5 months, the median independently reviewed PFS was 6.2 months in the combination arm vs 5.4 months in the placebo arm (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.45 to 0.70; P < .0001). With a minimum follow-up of 14.5 months, the median overall survival was 15.7 months in the combination arm vs 11.1 months in the placebo arm (HR, 0.70; 95% CI, 0.55 to 0.88; P = .0024). Treatment-related adverse events occurred in 98.2% of patients across both arms. There were 59.6% of patients in the combination arm and 56.4% of patients in the placebo arm who experienced a grade 3/4 treatment-related adverse events. Grade 5 treatment-related adverse events occurred in 2.6% of patients in the combination arm and 0.9% in the placebo arm.

Dr Hsu and coauthors concluded the tiragolumab, atezolizumab, and chemotherapy regimen “demonstrate[ed] statistically significant and clinically meaningful improvements in PFS and OS,” also noting there was a “generally consistent benefit…observed across subgroups, including PD-L1 status,” and “the safety profile was consistent with the known risks of the individual [treatments].”

ASCO expert Pamela Kunz, MD, added, “This phase 3 trial demonstrates that dual immunotherapy plus chemotherapy with the novel checkpoint inhibitor, tiragolumab, improves progression free and overall survival without compromising safety.”

Source:

Hsu CH, Lu Z, Gao S, et al. SKYSCRAPER-08: A phase III, randomized, double-blind, placebo-controlled study of first-line (1L) tiragolumab (tira) + atezolizumab (atezo) and chemotherapy (CT) in patients (pts) with esophageal squamous cell carcinoma (ESCC). Presented at 2024 ASCO Gastrointestinal Cancer Symposium; January 18-20, 2024; San Francisco, California. Abstract 245

New Immunotherapy Combinations for Patients with Esophageal Cancer. ASCO. January 16, 2024. https://old-prod.asco.org/about-asco/press-center/news-releases/new-immunotherapy-combinations-patients-esophageal-cancer.