Baiji state in 2019 European tumor
"The combination of tirelizumab and chemotherapy showed lasting remission and overall tolerance in this trial for patients with G/GEJ adenocarcinoma and ESCC," said Ben Yong, chief medical officer of cancer immunology in Baiji Shenzhou. gastric and esophageal cancer are among the most common cancer species in the world [1], with highly unmet treatment needs, especially in china [2], which is more prominent. We are pleased to be able to continue the late development of tirelizumab in these and other high-risk cancers in Asia.
This open, multicenter, china-initiated phase 2 clinical trial of tirelizumab combination standard chemotherapy as a potential first-line treatment (clinicaltrials.gov accession: nct03469557) included two patient cohorts, g/gej adenocarcinoma and escc. As of March 31,2019, a total of 30 patients were enrolled in the trial, including 15 patients with G/GEJ adenocarcinoma and 15 patients with ESCC. Patients with G/GEJ adenocarcinoma received a dose of 200 mg of tirelizumab and oxaliplatin on the first day of a cycle of three weeks, twice daily capecitabine on the first to 15 days, and ESCC patients received a dose of 200 mg of tirelizumab and cisplatin on the first to fifth days of a cycle of three weeks.
As of the data cutoff, eight patients were still receiving tirelizumab, including four patients with G/GEJ adenocarcinoma and four patients with ESCC. The results include:
At the data cut-off point, seven patients with G/GEJ adenocarcinoma (46.7%) achieved confirmed partial remission (PR), the objective remission rate of the cohort (ORR; sum of complete remission and partial remission) was 46.7%; seven patients with ESCC (46.7%) reached confirmed PR, and the ORR of the cohort was 46.7%; In the G/GEJ adenocarcinoma cohort, the median remission duration (DoR) was not yet mature; in the ESCC cohort, the median DoR was estimated at 12.8 months; The median progression-free survival (PFS) was 6.1 months in the G/GEJ adenocarcinoma cohort and 10.4 months in the ESCC cohort; Although median follow-up was longer in the G/GEJ adenocarcinoma cohort (15.4 months) and ESCC cohort (13 months), the median total survival period (OS) had not been achieved; in the G/GEJ adenocarcinoma cohort, the OS rate was 85 per cent at 6 months and 62 per cent at 12 months; in the ESCC cohort, the OS rate was 71 per cent at 6 months and 50 per cent at 12 months; terelizumab combined with standard first-line chemotherapy in G/GEJ adenocarcinoma and ESCC patients with overall tolerance. Adverse events (AE) were consistent with the tolerance of known PD-1 inhibitor combined chemotherapy. All patients experienced adverse events during treatment (TEAE), most of which were mildly or moderately severe; The most common levels of TEAE (incidence ≥40%) were anemia (60%), loss of appetite (56.7%), nausea (53.3%), weakness (50%), leukopenia (43.3%), vomiting (43.3%), decreased neutrophil count (40%) and thrombocytopenia (40%); Eleven patients (G/GEJ adenocarcinoma, n =6; ESCC, n =5) experienced tertiary TEAE, the most common of which were vomiting (16.7%), hyponatremia (13.3%), aspartate aminotransferase (AST) elevation, weight loss, loss of appetite, hypokalemia, anemia, leukopenia, neutropenia, and thrombocytopenia (each case); Severe adverse events (SAE) were experienced in 13 patients (G/GEJ adenocarcinoma, n =5; ESCC, n =8); severe TEAE in at least 2 patients (regardless of cohort) included increased blood bilirubin (G/GEJ adenocarcinoma, n =2), dysphagia (ESCC, n =3) and fatigue (ESCC, n =2); and one escc patient died due to ae (liver dysfunction), mainly due to disease progression, and may also be associated with trial treatment or potential hepatitis b infection.
On tirelizu monoclonal antibody:
terelizumab (bgb-a317) is a human-derived lg4 anti-programmed death receptor 1(pd-1) monoclonal antibody in research designed to minimize binding to fc receptors in macrophages. preclinical data suggest that fc receptors in macrophages after binding activate antibody-dependent cell-mediated killing of t cells, thereby reducing the antitumor activity of pd-1 antibodies. Terelizumab, the first candidate developed by the bio-platform for immune tumors in baiji state, is being developed as a single drug and combination therapy for a range of indications for solid tumors and blood tumors. The ongoing clinical study of tirelizumab includes a phase 3 clinical study for patients with second-line or third-line non-small cell lung cancer (NSCLC); a phase 3 clinical study for patients with first-line hepatocellular carcinoma (HCC); a phase 3 clinical study for patients with second-line squamous cell carcinoma of the esophagus (SCC); a phase 3 clinical study for patients with first-line gastric/gesophageal junction (G/GEJ) cancer; a phase 3 clinical study for first-line patients with SCC; and a phase 2 clinical study for patients with HCC from second to third-line. These clinical trials are recruiting patients in several countries and regions, including the United States, Europe and China.
In addition to a critical phase 2 clinical study for patients with recurrent/refractory (r/r) transtypical hodgkinundefineds lymphoma (chl) and a critical phase 2 clinical study for patients with locally advanced or metastatic urothelial carcinoma (uc), baiji state is conducting a phase 3 clinical study for patients with first-line non-squamous nsclc; a phase 3 clinical study for patients with first-line squamous nsclc; a phase 3 clinical study for patients with first-line nasopharyngeal carcinoma (npc); a phase 3 clinical study for patients with esc; and a phase 2 clinical study for patients with high-satellite instability (h) or repair of defective msmsclc (mmd). These clinical studies are mainly being carried out in China.
The china state drug administration (nmpa, formerly cfda) drug review center (cde) is reviewing new drug listing applications (nda) for tirelizumab for r/rchl patients and for patients with previously treated locally advanced or metastatic uc patients, both of which are included in the priority review. Baiji shenzhou has the global development and commercialization authorization of tirelizumab.
