EAST HANOVER, N.J.— Novartis announced today results from the pivotal Phase III RATIONALE 302 trial showing the investigational anti-PD-1 immune checkpoint inhibitor tislelizumab improved overall survival (OS) versus chemotherapy (median 8.6 months vs. 6.3 months, p=0.0001). The study evaluated tislelizumab in patients with unresectable recurrent locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) who had received prior systemic therapy. Results were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

Results from RATIONALE 302 in ESCC showed tislelizumab extended median OS by 2.3 months compared to chemotherapy with a 30% reduction in the risk of death (HR=0.70, 95% CI: 0.57-0.85, p=0.0001). In PD-L1 positive patients, tislelizumab extended median OS by 3.5 months with a 46% reduction in the risk of death (HR=0.54, 95% CI: 0.36-0.79, p=0.0006).

“These data show that tislelizumab has the potential to help patients with esophageal squamous cell carcinoma – one of the deadliest types of cancers – live longer,” said Jeff Legos, Senior Vice President and Head of Oncology Drug Development. “We are excited about these results from the newest asset in our portfolio of transformational medicines and look forward to sharing these data with regulatory authorities, as we continue to explore the full potential of this uniquely designed anti-PD-1 antibody.”

Treatment with tislelizumab demonstrated median progression-free survival (PFS) of 1.6 months compared to 2.1 months (HR=0.83, 95% CI: 0.67–1.01). Tislelizumab demonstrated a higher and more durable anti-tumor activity than chemotherapy (objective response rate [ORR], 20.3% vs. 9.8%; median duration of response [DoR], 7.1 months vs. 4.0 months).

The discontinuation rate due to treatment-related adverse events (TRAEs) was lower in patients who received tislelizumab (6.7%) compared to chemotherapy (13.8%). The most common all-grade TRAEs (≥10%) with tislelizumab were increased aspartate aminotransferase (11.4%), anemia (11%) and hypothyroidism (10.2%). No new safety signals were identified.

“Most patients with this type of esophageal cancer are diagnosed with advanced disease, resulting in a poor prognosis for this difficult-to-treat cancer,” said  Dr. Jaffer Ajani, professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center. “The impact tislelizumab had on survival compared to chemotherapy in this study is highly meaningful and encouraging news for patients, caregivers and treating oncologists.”

Esophageal squamous cell carcinoma is the most common type of esophageal cancer globally and the sixth leading cause of cancer-related death worldwide. Each year, esophageal cancer claims nearly as many lives as colon cancer across the globe. More than two-thirds of patients with ESCC have advanced or metastatic disease at the time of diagnosis.⁴ The average five-year survival rate is only five percent.⁵