AB122 is a fully human monoclonal antibody targeting PD-1. It binds tightly to a different PD-1 epitope than other currently approved antibodies in this class. Here we report preliminary data from an ongoing, open-label, dose-escalation (3 + 3 design) study evaluating the safety, tolerability, immunogenicity, pharmacokinetics, pharmacodynamics, and antitumor activity of AB122 monotherapy in patients (pts) with select advanced solid tumors.
Eligible pts had pathologically confirmed select advanced solid tumors, received ≤5 prior lines of systemic therapies, and had measurable disease per RECIST v1.1. AB122 was administered intravenously (IV) every 2 wks (Q2W) at escalating doses (80, 240, 720 mg). Intermediate Q2W doses and other schedules (every 3 wks [Q3W] or 4 wks [Q4W]) were also evaluated. Adverse events (AEs) were graded according to NCI CTCAE v4.03 and antitumor activity was assessed using RECIST v1.1.
As of 15Aug2018, 19 pts with advanced ovarian (n = 7), endometrial (n = 3), colorectal (n = 3), gastroesophageal (n = 2), head and neck, breast, prostate, and lung (n = 1 each) cancer were treated at doses of 80 mg Q2W (n = 3), 240 mg Q2W (n = 6), 360 mg Q2W (n = 1), 360 mg Q3W (n = 4), and 480 mg Q4W (n = 5). Most pts were female (74%) and White (89%); median age was 68 yrs (51-80). The number of doses received ranged from 1 to 18; 8 pts remain on study. The most common treatment-emergent AEs were fatigue (42%), diarrhea (21%), urinary tract infection, back pain, nausea, and anemia (16% each). 16% of pts each had ≥Grade 3 AEs and serious AEs but none were considered treatment-related by investigators. There were no dose-limiting toxicities or discontinuations due to AEs. Data from pts in the 80 and 240 mg Q2W cohorts showed that AB122 serum concentrations ≥1.5 μg/mL (equivalent to 10 nM) are associated with full receptor occupancy. Among 12 efficacy-evaluable pts, the disease control rate was 42%.
These preliminary results indicate that AB122 monotherapy was well tolerated and active in various advanced solid tumor types. The dose and schedule of 240 mg IV Q2W were selected for further evaluation as monotherapy and in combination with other agents.
Arcus Biosciences, Inc.
Arcus Biosciences, Inc.
L.C. Seitz, W. Berry, D. Ashok, D. Direnzo, L. Jin, S.J. Lee, A. Park, D. Piovesan, J. Karakunnel: Employee of Arcus Biosciences, Inc. A. Rieger, J.B.L. Tan, M.J. Walters: Employee of Arcus Biosciences, Inc.