In a phase III study, Novartis’ experimental checkpoint inhibitor tislelizumab improved overall survival in patients with esophageal squamous cell carcinoma.
Results of phase III trial show that Novartis’ experimental anti-PD-1 immune checkpoint inhibitor, tislelizumab, improved overall survival (OS) in patients with esophageal cancer versus chemotherapy. The phase III RATIONAL 302 study evaluated tislelizumab in patients with unresectable relapsed locally advanced or metastatic squamous cell carcinoma of the esophagus (ESCC) who had received prior systemic therapy.
Results of RATIONAL 302 in ESCC showed that tislelizumab prolonged median OS by 2.3 months compared to chemotherapy (median 8.6 months vs 6.3 months, respectively) and reduced the risk of death by 30 percent. In PD-L1-positive patients, tislelizumab prolonged the median OS by 3.5 months, with a 46 percent reduction in the risk of death (Hazard Ration [HR] = 0.54).
“These data demonstrate that tislelizumab has the potential to help patients with squamous cell carcinoma of the esophagus – one of the deadliest cancers – live longer,” said Dr. Jeff Legos, Senior Vice President and Head of Oncology Drug Development at Novartis. “We are excited about these results from the latest addition to our transformational drug portfolio and look forward to sharing this data with regulatory authorities as we continue to explore the full potential of this uniquely designed anti-PD-1 antibody.”
Treatment with tislelizumab resulted in a median progression-free survival (PFS) of 1.6 months compared to 2.1 months (HR = 0.83). Tislelizumab demonstrated higher and more durable antitumor activity than chemotherapy (objective response rate [ORR] = 20.3 percent vs. 9.8 percent; median duration of response [DoR] = 7.1 months versus 4.0 months).
The discontinuation rate due to treatment-related adverse events (TRAEs) was lower in patients receiving tislelizumab (6.7 percent) compared to chemotherapy (13.8 percent). The most common all-grade TRAEs (≥10 percent) with tislelizumab were elevated aspartate aminotransferase (11.4 percent), anemia (11 percent) and hypothyroidism (10.2 percent). No new safety signals were identified.
“Most patients with this type of esophageal cancer are diagnosed with advanced disease, which results in a poor prognosis for this difficult-to-treat cancer,” said Dr. Jaffer Ajani, professor of Gastrointestinal Medical Oncology at the University’s MD Anderson Cancer Center of Texas, US. “The impact tislelizumab had on survival compared to chemotherapy in this study is very meaningful and encouraging news for patients, healthcare providers and treating oncologists.”
Squamous cell carcinoma of the esophagus is the most common form of esophageal cancer worldwide and the sixth leading cause of cancer death worldwide. Every year, esophageal cancer claims nearly as many lives worldwide as colon cancer. More than two-thirds of patients with ESCC have advanced or metastatic disease at the time of diagnosis. The average five-year survival rate is only five percent.
Tislelizumab has been specifically formulated to minimize binding to macrophage Fcγ receptors, a potential mechanism of anti-PD-1 resistance.
In an agreement completed earlier this year, BeiGene granted Novartis the rights to develop, manufacture and market tislelizumab in North America, Europe and Japan through a collaboration and licensing agreement.