Efficacy and safety of geptanolimab (GB226) for relapsed or refractory peripheral T cell lymphoma: an open-label phase 2 study (Gxplore-002)

Abstract

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 PTCL 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. Results Between July 12, 2018, and August 15, 2019, 102 patients were enrolled and received at least one dose of geptanolimab. At the data cutoff date (August 15, 2020), the median follow-up was 4.06 (range 0.30–22.9) months. For 89 patients in FAS, 36 achieved objective response (40.4%, 95% CI 30.2–51.4), of which 13 (14.6%) were complete response and 23 (25.8%) had partial response assessed by IRRC. The median duration of response (DOR) was 11.4 (95% CI 4.8 to not reached) months per IRRC. Patients with PD-L1 expression ≥ 50% derived more benefit from geptanolimab treatment compared to < 50% ones (ORR, 53.3% vs. 25.0%, p = 0.013; median PFS 6.2 vs. 1.5 months, p = 0.002). Grade ≥ 3 treatment-related adverse events occurred in 26 (25.5%) patients, and the most commonly observed were lymphocyte count decreased (n = 4) and platelet count decreased (n = 3). Serious adverse events were observed in 45 (44.1%) patients and 19 (18.6%) were treatment related. Conclusions In this study, geptanolimab showed promising activity and manageable safety profile in patients with r/r PTCL. Anti-PD-1 antibody could be a new treatment approach for this patient population. Trial registration: This clinical trial was registered at the ClinicalTrials.gov (NCT03502629) on April 18, 2018.

The changing landscape of anti-lymphoma drug clinical trials in mainland China in the past 15 years (2005–2020): A systematic review

“…In 2014, with promising data of a pivotal phase II study [29] , the Chinese original innovative HDACi chidamide has been approved for the treatment of r/r PTCL. Recently, the result of a phase II clinical trial showed that an innovative anti-PD-1 antibody geptanolimab (GB226) has showed potent activity in r/r PTCL, which may provide new treatment approach for r/r PTCL patients [30] . Second, newer targets have emerged in registered clinical trials.…”

B7 Family Members in Lymphoma: Promising Novel Targets for Tumor Immunotherapy?

“…The ORR of pembrolizumab in patients with ENKTL was 78.6% (12). A recent study reported that geptanolimab showed promising efficacy and manageable toxicity in patients with relapsed/refractory peripheral T cell lymphoma (13). Interestingly, patients with PD-L1 expression > 50% obtained more benefit from geptanolimab treatment, with an ORR of 53.3% and a median progression-free survival of 6.2 months (13).…”

“…A recent study reported that geptanolimab showed promising efficacy and manageable toxicity in patients with relapsed/refractory peripheral T cell lymphoma (13). Interestingly, patients with PD-L1 expression > 50% obtained more benefit from geptanolimab treatment, with an ORR of 53.3% and a median progression-free survival of 6.2 months (13). The correlations between PD-L1 expression and response to anti-PD-1 antibodies should to be further investigated in future clinical trials.…”

Toxicity of Immune-Checkpoint Inhibitors in Hematological Malignancies

“…Arthralgia and myalgia are the most frequently reported rheumatic irAEs, but arthritis, myositis and vasculitis were observed in blood cancer ICI trials as well (Bashey et al, 2009;Khodadoust et al, 2016;Zeidan et al, 2018;Armand et al, 2019;Barta et al, 2019;D'Souza et al, 2019;Davids et al, 2020;Diefenbach et al, 2020;Mei et al, 2020;Song et al, 2020;Liu et al, 2021;Shi et al, 2021). (Table 6) These adverse events are more likely to occur in ICIs acting on the PD-1 axis and may have later onset (Chhabra and Kennedy, 2021).…”

“…One patient with RR mycosis fungoides/ Sézary syndrome who was receiving pembrolizumab experienced grade 3 corneal ulcer (Khodadoust et al, 2016). Incidents of autoimmune hematologic toxicity included newly diagnosed immune thrombocytopenia during ipilimumab therapy, autoimmune hemolytic anemia grade 4 during geptanolimab therapy (anti-PD-1 mAb) and one grade 3 and one lethal case of hemophagocytic lymphohistiocytosis in clinical studies investigating pembrolizumab monotherapy in T cell lymphomas and the combination of nivolumab with azacitidine for acute myeloid leukemia patients, respectively (Davids et al, 2016;Barta et al, 2019;Daver et al, 2019;Shi et al, 2021). (Table 6)…”