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.

• DOI: 10.1200/jco.2017.35.15_suppl.3013
• Publication Date: 2018-09-06T15:41:22Z
• Authors: Michael Friedlander; Tarek Meniawy; Ben Markman; Linda R. Mileshkin; Paul R. Harnett; Michael Millward; Joanne Lundy; Alison E. Freimund; Christie Norris; Song Mu; John Wu; Virginia E. Paton; Lai Wang; Bo Gao
• Keywords: 0301 basic medicine; 03 medical and health sciences; 3. Good health

3013 Background: The release of tumor-associated antigens may enhance the response to immunotherapy. BGB-A317, a humanized IgG4 variant monoclonal antibody engineered have no Fc gamma receptor binding, targets programmed cell death-1 (PD-1) receptor. It is being developed in solid and hematologic malignancies at dose 200 mg IV Q3W. BGB-290, potent inhibitor PARP 1/2, hypothesized promote neoantigen that will potentially increase efficacy BGB-A317. A phase 1 study identified 60mg BID as recommended Phase 2 (RP2D) for BGB-290. This consists initial escalation determine maximum-tolerated (MTD), safety, PK profile, preliminary anti-tumor activity combination, followed by expansion into ovarian, breast, prostate, gastric, bladder, pancreatic small lung cancers. Methods: Cohorts 6 -12 pts with advanced tumors were treated each 5 planned levels (DLs). In DLs 1-3, BGB-290 doses ranged between 20-60mg PO BGB-A317 2mg/kg 4 - 5, 40 or 60 BID; A317 was given Q3W based on data from single agent study. Results: As 16 Jan 2017, 38 [median age 59 years (34-75)] 1-4; enrollment DL5 ongoing. One DLT persistent Gr nausea reported DL 4. most common adverse event (AE) considered related both drugs fatigue (10.5%). Immune-related AEs 3 hypophysitis (n = 1), autoimmune hepatitis(n 2), elevated AST/ALT 1). Decreases tumor burden been observed pts; 7 achieved PR (5 ovarian one uterine cancer) CR cancer. Six had SD > months including cancer who received BGB-A317+BGB-290 189 281 days. Plasma/serum exposure consistent those single-agent trials. Conclusions: BGB290 can be combined. Dose multiple types commence 2017 once RP2D determined. Clinical trial information: NCT02660034.