Penpulimab, an anti-PD-1 antibody, for heavily pretreated metastatic nasopharyngeal carcinoma: a single-arm phase II study

Abstract

Penpulimab is an anti-programmed cell death-1 (PD-1) IgG1 antibody with no Fc gamma receptor (FcγR) binding activity, and thus theoretically reduced immune-related adverse events (irAEs) while maintaining efficacy. This single-arm, phase II trial conducted across 20 tertiary care centers in China enrolled adult patients with metastatic nasopharyngeal carcinoma (NPC) who had failed two or more lines of previous systemic chemotherapy. Patients received 200-mg penpulimab intravenously every 2 weeks (4 weeks per cycle) until disease progression or intolerable toxicities. The primary endpoint was objective response rate (ORR) per RECIST (version 1.1), as assessed by an independent radiological review committee. The secondary endpoints included progression-free survival (PFS) and overall survival (OS). One hundred thirty patients were enrolled and 125 were efficacy evaluable. At the data cutoff date (September 28, 2022), 1 patient achieved complete response and 34 patients attained partial response. The ORR was 28.0% (95% CI 20.3-36.7%). The response was durable, with 66.8% still in response at 9 months. Thirty-three patients (26.4%) were still on treatment. The median PFS and OS were 3.6 months (95% CI = 1.9-7.3 months) and 22.8 months (95% CI = 17.1 months to not reached), respectively. Ten (7.6%) patients experienced grade 3 or higher irAEs. Penpulimab has promising anti-tumor activities and acceptable toxicities in heavily pretreated metastatic NPC patients, supporting further clinical development as third-line treatment of metastatic NPC.

Fig. 1

The study flowchart. PD progressive disease

Fig. 2

Treatment response and survival outcomes. a Waterfall plot of the best percentage changes for the sum of target lesion diameters for patients received at least one time of radiographic evaluation. *This patient had a >20% increase in the sum of diameter, but with absolute increase <5 mm, per the IRRC and, therefore, stable disease (SD) was documented instead of progressive disease (PD). ^The indicated lesion in this patient is lymph node. b Swimmer plots of time to tumor response (months) of individual patients with metastatic nasopharyngeal carcinoma as assessed by the independent radiological review committee (IRCC) according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Each swim lane represents one patient in the full-analysis set (FAS) per IRRC. Patient responses are color coded. CR complete response, NE not evaluable, PD progressive disease, PR partial response, SD stable disease. Kaplan–Meier-estimated progression-free survival (PFS) curves (c) and overall survival (OS) curves (d) of NPC patients in the FAS per IRRC

Fig. 3

Survival outcomes stratified by key baseline characteristics. Kaplan–Meier-estimated progression-free survival (PFS) curves and overall survival (OS) curves of NPC patients stratified by PD-L1 expression (TPS ≥ 50% vs. <50%) (a, b) and (TPS ≥ 1% vs. < 1%) (c, d), EBV DNA levels (≥ 500 IU/mL vs. <500 IU/mL) (e, f), and baseline lactate dehydrogenase (LDH) levels (≥the upper limit, ULN vs. <ULN) (g, h)