Penpulimab is a humanized IgG1 mAb that blocks PD-1 binding to PD-L1, Penpulimab is engineered to eliminate FcγR binding and ADCC/ADCP completely, as compared to majority of marketed IgG4 PD-1 antibodies with ADCC/ADCP activity. Penpulimab demonstrats a slower PD-1 antigen binding off-rate than marketed PD-1 antibodies, which results in better cellular activity and higher receptor occupancy. Penpulimab also shows numerous contacts with N58 glycosylation on the BC loop of PD-1 which could be an advantage to facilitate interaction of PD-1 antibody. These structural differentiations offer more robust biological effect and enhance anti-tumor activity of Penpulimab.
This integrated safety analysis includes data from 422 patients (pts) treated with monotherapy or combination therapy of Penpulimab from 6 clinical trials: one dose-escalation and expansion study [AK105-101(in advanced solid tumor) treated with single dose of 1.0, 3.0, 10 mg/kg and 200mg Q2W] in Australia and 5 studies [AK105-201 (in R/R cHL), AK105-202 (in NPC) and AK105-204 (in advanced solid tumor) treated with 200mg Q2W monotherapy; AK105-203 (in HCC) treated with Penpulimab 200mg Q3W combined with Anlotinib 8mg d1-14 Q3W; AK105-301( in non-squamous NSCLC) treated with Penpulimab 200mg Q3W combined with chemotherapy] in China. In this analysis, immune-related adverse events (irAEs) of Penpulimab is based on suspected irAEs confirmed by medical review.
As of Jan 10 2020, a total of 422 patients (pts) [monotherapy: combo therapy= 329:93] received a median of 8 doses [1-52] of Penpulimab. Main types of tumor (≥10 pts) in this analysis include: R/R cHL (N=94), NPC (N=89), NSCLC (N=56), HCC (N=53), gastric/GEJ cancer (N=21), ovarian cancer (N=20), pancreatic cancer(N=11), esophageal cancer (N=11) and biliary duct carcinoma (N = 11). irAEs occurred in 23.0% of pts (G3 in 2.6%, no G4 or G5, serious in 0.7%, treatment discontinuation in 0.7%). Most common irAEs (≥1%) were hypothyroidism (9.2%), hyperthyroidism (4.3%), increased TSH (2.8%) and rash (2.4%).
Penpulimab demonstrates impressive safety profile with relatively lower incidence rate of ≥ Grade 3 immune-related adverse events.
Clinical trial identification
NCT03352531, NCT03722147, NCT03866967, NCT04172571, NCT04172506, NCT03866980.
Legal entity responsible for the study
Y. Xia, D. Xia, X. Jin, Z.M. Wang, B. Li: : Honoraria (self): Akeso, Inc. All other authors have declared no conflicts of interest.