Efficacy and Safety of Geptanolimab (GB226) for Relapsed or Refractory Peripheral T-Cell Lymphoma: An Open-Label Phase 2 Study (Gxplore-002)

Background: Peripheral T cell lymphoma (PTCL) is a rare disease and recent approved drugs for relapsed/refractory (r/r) PTCL provided limited clinical benefit. We conducted this study to evaluate the efficacy and safety of geptanolimab (GB226), an anti-PD-1 antibody, in r/r PTCL patients. Methods: We did this single-arm, multicenter phase 2 study across 41 sites in China. Eligible patients with r/r PTCL received geptanolimab 3 mg/kg intravenously every 2 weeks until disease progression or intolerable toxicity. All patients who received at least one dose of geptanolimab and histological confirmed entered full analysis set (FAS). The primary endpoint was objective response rate (ORR) in FAS assessed by the independent radiological review committee (IRRC) per Lugano 2014 criteria.  Findings: Between July 8, 2018 and August 15, 2019, 102 patients were enrolled and received at least one dose of geptanolimab. At data cutoff (Feb 15, 2020), the median follow-up was 4.06 months (range: 0.30-16.7). For 84 patients in FAS, 33 achieved objective response (39.3%, 95% CI 28.80-50.55), of which 10 (11.9%) were complete response and 23 (27.4%) had partial response assessed by IRRC. The 6-month duration of response (DOR) rate was 61.8% (95% CI 41.4, 76.9). Patients with PD-L1 expression ≥50% derived more benefit from geptanolimab treatment compared to <50% ones (ORR, 51.2 vs. 24.2%, p=0.020; median PFS 6.2 vs. 1.4 months, p=0.015). Grade ≥3 treatment-related adverse events occurred in 24 (23.5%) patients; and the most commonly observed were lymphocyte count decreased (n=4) and platelet count decreased (n=4). Serious adverse events were observed in 39 (38.2%) patients and 16 (15.7%) were treatment-related. Interpretation: In this study, geptanolimab showed potent activity with a manageable safety profile. Immune checkpoint inhibitor can be a new treatment approach for patient with r/r PTCL. Trial Registration: This trial was registered at the ClinicalTrials.gov (NCT03502629). Funding: Genor Biopharma Co., Ltd., China National Major Project, and Chinese Academy of Medical Sciences Declaration of Interests: FX and QW are employees of Genor Biopharma Co., Ltd., China. The other authors declared no conflicts of interest. Ethics Approval Statement: The protocol, protocol amendments, and patient informed consent were reviewed and approved by the relevant independent ethics committee at each participating centre prior to implementation. Written informed consent was obtained from all patients prior to enrolment.