A phase I study of APL-501, an anti-PD-1 antibody, in patients with recurrent or advanced solid tumors.

Abstract

e15125 Background: APL-501 is a humanized monoclonal antibody targeting programmed cell death-1 (PD-1). APL-501 is being evaluated in patients (pts) with advanced recurrent and relapsed solid tumors who had not been previously treated with an immune checkpoint inhibitor in an ongoing 3-part Phase 1 trial (NCT03053466). Herein, we present the emerging pharmacokinetic (PK) and receptor occupancy (RO), safety and preliminary efficacy. Methods: Weight-based dose escalation (1, 3, and 10 mg/kg, Part 1) and Extension (Part 2) has been completed and the study is currently enrolling specific tumor types (MSI-H/dMMR and Carcinoma of Unknown Primary [CUP]) into the Expansion Cohorts (Part 3). Relapsed/refractory solid tumor pts were enrolled in Part 1 and Part 2. Key exclusion criteria included prior therapy targeting PD-1/PD-L1 and uncontrolled CNS metastases. APL-501 was administered IV over 1 hour every 14 days. Serum and PBMCs were collected for PK and RO analysis, respectively. RO was assessed using different T-cell markers measured by flow cytometry of PBMC. Anti-tumor activity was assessed by investigators using RECIST and irRECIST. Safety was assessed using CTCAE, v4.03. Results: As of 31 Dec 2019, 22 pts were enrolled with a mean age of 62.1 (SD: 12.2) years. ECOG PS 0/1 reported at 10/12 pts, respectively. Pts had a median number of 3 prior lines of therapy (range, 1 – 9) and median time to treatment from initial diagnosis was 30.1 months (range, 6.7 – 184.8). Across doses evaluated, APL-501 demonstrated dose proportional PK. One hundred percent (100%) RO was observed across all doses evaluated. No dose limiting toxicities were reported. Fifteen pts (68.2%) had related AEs; two pts (9.1%) had Grade ≥ 3 related AEs to APL-501. Eight pts had stable disease and two pts had partial response by RECIST (esophageal adenocarcinoma and CUP). Seven pts remained on therapy for ≥ 24 weeks. The recommended phase 2 dose (RP2D) has been determined to be 400 mg IV every 14 days (non-weight-based) based on safety and PK modeling. Conclusions: Preliminary results indicate clinical activity of APL-501 in relapsed/refractory malignant disease with a generally tolerable safety profile. The PK and RO profile, across all doses evaluated, appears comparable to marketed PD-1 inhibitors. Continued exploration of APL-501 with the RP2D in CUP and MSI-H/dMMR tumors is being planned. Clinical trial information: NCT03053466 .