Preliminary results from a phase 1 study of AB122, a programmed cell death-1 (PD-1) inhibitor, in patients with advanced solid malignancies

Abstract

Background: 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. Methods: Eligible pts had pathologically confirmed select advanced solid tumors, received ≤5 prior lines of systemic therapies, and hadmeasurable disease per RECIST v1.1. AB122 was administered intravenously (IV) every 2 wks (Q2W) at escalating doses (80, 240 720mg). IntermediateQ2Wdoses and other schedules (every 3 wks [Q3W] or 4 wks [Q4W]) were also evaluated. Adverse events (AEs) were graded according toNCI CTCAE v4.03 and antitumor activity was assessed using RECIST v1.1. Results: 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 80mgQ2W(n=3), 240mgQ2W(n=6), 360mg Q2W(n=1), 360mgQ3W(n=4), and 480mgQ4W(n=5).Most pts were female (74%) and White (89%);median age was 68 yrs (51-80). The number of doses received rangedfrom1 to 18; 8 pts remainonstudy. Themost 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 andserious AEs butnonewere considered treatment-related by investigators. There were no dose-limiting toxicities or discontinuations due to AEs. Data frompts in the 80 and 240mgQ2Wcohorts showed that AB122 serumconcentrations≥1.5 lg/mL (equivalent to 10 nM) are associated with full receptor occupancy. Among 12 efficacy-evaluable pts, the disease control rate was 42%. Conclusions: 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.