Date: 2017-04-21
Type of
information: Presentation of results at a congress
phase: 1b
Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago
Company: BeiGene (China)
Product: BGB-290 and BGB-A317
Action
mechanism:
- poly ADP ribose polymerase PARP inhibitor/PARP inhibitor/monoclonal antibody/immune checkpoint inhibitor. BGB-290 is an oral, selective and potent inhibitor of poly (ADP-ribose) polymerase (PARP), an enzyme family which is involved in a number of cellular processes, including DNA repair and programmed cell death.
- BGB-A317 is an anti PD-1 monoclonal antibody. BGB-A317 is being developed as a monotherapy and in combination with other therapies for the treatment of various cancers.
Disease: advanced solid tumors
Therapeutic
area: Cancer - Oncology
Country: Australia
Trial
details:
- The multicenter, open-label Phase 1/1b study is evaluating the combined use of BGB-A317 and BGB-290. The dose escalation phase is designed to establish the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose, evaluate the pharmacokinetics (PK) of the drug combination, and assess the immunogenicity of BGB-A317. The dose expansion phase is designed to further evaluate the tolerability and activity of the combination in patients with advanced solid tumors likely to harbor DNA damage repair deficiencies or who may be susceptible to treatment either with a PARP inhibitor or with PD-1 blockade. (NCT02660034)
Latest
news:
- • On June 5, 2017, BeiGene presented initial data from the dose escalation portion of the Phase 1 trial of anti-PD-1 antibody BGB-A317 in combination with PARP inhibitor BGB-290 in patients with advanced solid tumors at the 2017 American Society for Clinical Oncology (ASCO) Annual Meeting. The preliminary data suggest that the combination of BGB-A317 and BGB-290 is generally well-tolerated and shows anti-tumor activity in multiple solid tumors.
- At the data cut-off of March 31, 2017, 43 patients were enrolled in the dose-escalation portion of the trial. Cohorts of six to 12 patients each received treatments at five planned dose levels. BGB-A317 was administered at 2 mg/kg every three weeks (Q3W) with BGB-290 at 20, 40, or 60 mg twice daily in dose levels 1, 2, and 3, respectively. BGB-A317 was also administered at a fixed dose of 200 mg Q3W with BGB-290 at 40 or 60 mg twice daily in dose levels 4 and 5, respectively. Duration of treatment was greater than 200 days for 10 patients, and a total of seven patients remained on treatment as of the data cut-off.
- The safety analysis suggested that the combination of BGB-A317 and BGB-290 was generally well-tolerated in patients with advanced solid tumors. Dose-limiting toxicities occurred in three patients; these included one patient with grade 2 nausea at DL4, one patient with grade 2 nausea and grade 2 vomiting at DL5, and one patient with grade 4 autoimmune hepatitis at DL5. DL4 was determined to be the maximum tolerated dose.
- Grade 3 or 4 adverse events (AEs) assessed by the investigator to be related to BGB-A317 and reported in more than one patient included autoimmune hepatitis / hepatitis (12%) and elevated alanine aminotransferase (ALT) (5%). Grade 3 or 4 AEs assessed by the investigator to be related to BGB-290 and reported in more than one patient included anemia (14%), as well as elevated ALT, elevated aspartate aminotransferase (AST), fatigue, and nausea (5% each). Suspected immune-related AEs (irAEs) of any grade regardless of causality occurred in 17 patients (40%); those reported in at least two patients included elevated ALT/AST or gamma-glutamyltransferase (GGT), autoimmune hepatitis, diarrhea, hypothyroidism, and hyperthyroidism.
- Grade 3-4 liver-related events regardless of causality were reported in eight patients, including five patients with hepatitis and three patients with ALT and/or AST elevations. Together, liver-related AEs of any grade regardless of causality were observed in 12 patients; all events were reversible with or without corticosteroid treatment. Treatment with both agents was discontinued by 33 patients for reasons including disease progression (26 patients), AEs (seven patients), and / or consent withdrawal (two patients). There were no fatal adverse events.
- Co-administration of BGB-A317 with BGB-290 did not have a significant impact on the pharmacokinetic profile of either compound. In 29 patients with ovarian or fallopian tube cancer, best responses included one confirmed complete response , two confirmed partial responses, five unconfirmed partial responses, and seven cases of stable disease. In two patients with breast cancer, best responses included one confirmed partial response. In three patients with pancreatic cancer, best responses included one unconfirmed partial response and two cases of stable disease. The one patient with uterine cancer had a best response of an unconfirmed partial response. Stable disease was observed in one of three patients with prostate cancer and the one patient with bile duct cancer. Additional tumor types enrolled in the study include bladder, cervical, lung, and peripheral nerve sheath cancer, with one patient each.
- The trial will further evaluate the combination’s activity in expansion cohorts of patients with ovarian, triple-negative breast, castration-resistant prostate, small cell lung, gastric / gastro-esophageal junction, urothelial, and pancreatic cancers.
- • On April 21, 2017, BeiGene announced that preliminary data from a Phase Ib combination study of its anti PD-1 antibody BGB-A317 and its PARP inhibitor BGB-290 in patients with advanced solid tumors will be presented in a poster discussion session at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting. The ASCO Annual Meeting will take place June 2–6, 2017 in Chicago, Illinois. Details of the presentation are provided below. Abstract #3013: A Phase 1b Study of the Anti-PD-1 Monoclonal Antibody BGB-A317 (A317) in Combination with the PARP Inhibitor BGB-290 (290) in Advanced Solid Tumors. Presenter: Michael Friedlander, MD, PhD.
Is
general: Yes
