A Phase Ib/II Clinical Trial of Linperlisib Combined with Camrelizumab and Pegaspargase in Advanced or Relapsed/Refractory NK/T-Cell Lymphoma: Analysis of the Phase Ib Part

Background:

NK/T-cell lymphoma (NKTCL) is highly aggressive, prevalent in Asia, and patients with advanced or relapsed/refractory NKTCL have dismal prognosis. Previous studies have shown promising results using PD-1/PD-L1 blockade, but the complete remission (CR) rate is unsatisfactory. Linperlisib, a novel selective PI3Kδ inhibitor, proved to be effective in relapsed/refractory T-cell lymphoma. It is uncertain whether combination of linperlisib, camrelizumab (PD-1 blockade) and pegaspargase will further improve the prognosis of advanced or relapsed/refractory NKTCL.

Methods:

This is a prospective, single-arm, single-center Ib/II clinical trial that included an initial safety run-in phase with safety monitoring before the main enrollment (expansion phase) (NCT06376721). The aim of phase Ib is to evaluate the recommended phase 2 dose and dose-limiting toxicity (DLT), and the aim of phase II study is to evaluate, for the first time, the safety and efficacy of the treatment of Linperlisib combined with PD-1 blockade Camrelizumab and Pegaspargase in patients diagnosed with advanced or r/r NKTCL, respectively. For the phase 1b study, qualified patients with refractory or relapsed NKTCL after initial remission, or Ann-Arbor stage III-IV de novo NKTCL were given linperlisib at the dosage of 80 mg/d, QD; Camrelizumab, 200 mg/d, Q3W; and Pegaspargase, 2500 IU/m², Q3W. Oral sulfanilamide was mandated to prevent pneumocystis infection. Six patients were needed in this phase 1b study, and the RP2D of linperlisib will be 80mg/d QD if no DLT occurred. DLT is defined as grade 4 myelosuppression or ≥ grade 3 non-hematologic adverse events.

Results:

Six patients were enrolled in this phase 1b study, all of whom had relapsed/refractory NKTCL and failed previous pegaspargase-based regimens. The median age was 50 years old (28-64), and all were male patients. Three patients had stage IV disease and the remaining three had stage IIE disease. All but one had systemic B symptoms, mainly featured by repeated high fever. One patient had concurrent hemophagocytic syndrome (HPS). All six patients were treated with the recommended dosage of linperlisib (80 mg/d QD), camrelizumab, and pegaspargase. A median of 2.5 cycles (2-4) and a total of 17 cycles of treatment were given. All patients were evaluated for efficacy after two cycles of therapy. No DLT occurred for all patients and all cycles. One patient had grade one leukopenia, and another one patient got COVID-19 infection, and both patients recovered after supportive care. Thus, the RP2D of linperlisib will be 80 mg/d QD. Concerning efficacy after two cycles of therapy, three patients obtained partial remission (PR), two patients had stable disease (SD), and one patient had disease progression, resulting in an ORR of 50% and disease control rate (DCR) of 83.3%. Now, the phase II study is ongoing.

Conclusions:

Linperlisib combined with camrelizumab and pegaspargase was well tolerated and efficacious in patients with advanced or relapsed/refractory NK/T-cell Lymphoma. The efficacy and safety profiles will be verified in the ongoing phase II study.

No relevant conflicts of interest to declare.

Linperlisib, a novel PI3K inhibitor, is approved in China for the treatment of relapsed/refractory Follicular Lymphoma. In this study, linperlisib was used in patients with NK/T-cell lymphoma as off-lable.