BeiGene announces results on Tislelizumab from ongoing clinical trials
BeiGene announced clinical results on its investigational anti-PD-1 antibody tislelizumab from three ongoing clinical trials in China. This open-label, multi-cohort, Phase 2 trial of tislelizumab in combination with chemotherapy as first-line treatment for patients with advanced lung cancer is being conducted in China. Patients with non-squamous non-small cell lung cancer were treated with tislelizumab at a dose of 200mg and doublet chemotherapy on day one of each three-week cycle; chemotherapy was given for up to four cycles, with pemetrexed and tislelizumab continued as scheduled if clinically appropriate. Patients with squamous NSCLC and small cell lung cancer were treated with tislelizumab at a dose of 200mg and doublet chemotherapy every three weeks, for four-six cycles, with tislelizumab continued as scheduled if clinically appropriate. As of February 25, 2019, 54 patients had received tislelizumab, with a median duration of treatment of 38.4 weeks. Fourteen patients remained on treatment as of the data cutoff. Results included the confirmed overall response rate across all cohorts of 66.7%, with ORRs of 43.8% in patients with non-squamous NSCLC; 80.0% in patients with squamous NSCLC; 66.7% in patients with squamous NSCLC; and 76.5% in patients with SCLC; Median progression-free survival was measured at a later data cutoff on June 30, 2019, and was 9.0 months in patients with non-squamous NSCLC, 7.0 months in squamous NSCLC, 6.9 months in SCLC, and in squamous NSCLC the median PFS had not yet been reached; At the median follow-up of 15.3 months, overall survival in patients with SCLC was 15.6 months; OS in other cohorts had not yet been reached; Treatment-emergent adverse events occurred in all 54 patients; adverse events reported as related to tislelizumab occurred in 46 patients, and seven patients discontinued tislelizumab treatment due to AEs; fourteen patients experienced at least one serious TEAE; one patient with squamous NSCLC had a fatal AE of immune-mediated myositis/rhabdomyolysis/cardiomyopathy after one dose of tislelizumab. The open-label, multi-cohort, Phase 2 trial of tislelizumab in combination with chemotherapy as first-line treatment for patients with advanced esophageal, gastric or gastroesophageal junction carcinoma is being conducted in China. Patients were treated with tislelizumab at a dose of 200mg and cisplatin on day one, and fluorouracil on days one through five during each 21-day cycle. At the time of data cutoff on March 31, 2019, 15 patients with ESCC had received treatment with tislelizumab, and four remained on treatment. Results included seven patients achieving a confirmed partial response and the ORR was 46.7%; Median duration of response was 12.8 months; median PFS was 10.4 months; Despite a median follow-up of 13.0 months, median OS had not been reached; AEs reported in this cohort were consistent with the safety profile of tislelizumab observed in previous studies with other tumor types and were generally of low severity; AEs reported in this cohort were consistent with the known tolerability profile of PD-1 inhibitors in combination with chemotherapy. The multi-center, open-label Phase 1/2 trial of tislelizumab as monotherapy in patients with advanced solid tumors is being conducted in China and consists of a Phase 1 dose verification and pharmacokinetics component, and a Phase 2 indication expansion in disease-specific cohorts, including patients with non-small cell lung cancer, melanoma, urothelial carcinoma, renal cell carcinoma, esophageal squamous cell carcinoma, gastric cancer, hepatocellular carcinoma, and microsatellite instability-high/mismatch repair deficient solid tumors. As of December 1, 2018, 300 patients across all indications had been treated in this study with tislelizumab at a dose of 200mg every three weeks. Tislelizumab was generally well tolerated among patients with advanced solid tumors. One patient with GC experienced a fatal brain edema, which was considered possibly related to tislelizumab treatment by the investigator.