Abstract 2110
Background
CS1001 is a first full-length, fully human anti-PD-L1 mAb developed by the OMT transgenic rat platform, which mirrors natural IgG4 human antibody with expected pharmacokinetics (PK) profiles, and may potentially reduce the risk of immunogenicity and toxicity in pts. This first-in-human Phase Ia/Ib study of CS1001 was conducted to evaluate the safety, tolerability, PK profile, and anti-tumor activity of CS1001 in pts with advanced solid tumors or lymphomas.
Methods
Pts with advanced solid tumors or lymphomas were enrolled in the dose escalation Phase Ia, receiving CS1001, Q3W, IV, at escalating doses from 3, to 10, 20, 40 mg/kg and 1200 mg fixed dose. Dose escalation followed a 3 + 3 dose escalation scheme. Dose-limiting toxicity (DLT) was evaluated within 3 weeks after the initial dose. Pts with various tumor types were enrolled in the dose expansion Phase Ib to assess anti-tumor activity and safety, including GC, cholangiocarcinoma, NSCLC, HCC, etc. Safety was assessed by monitoring the frequency and severity of adverse events (AEs) per NCI CTCAE v4.03, tumor response was assessed per RECIST v1.1 (solid tumors) or Lugano 2014 (lymphomas).
Results
As of 30 Nov 2018, 29 pts, median age of 53 (23-75) years, were enrolled in Phase Ia, 3 mg/kg (N = 3); 10 mg/kg (4); 20 mg/kg (3); 40 mg/kg (3) and 1200 mg fixed dose (16). 20 pts discontinued treatment, mostly due to disease progression (14). 2 pts discontinued treatment due to AEs (Grade [G] 4 hepatic function abnormal and G3 pulmonary tuberculosis, neither of which were related to CS1001). Median treatment duration was 126 (21-408+) days. No DLTs were observed. The most frequent TRAEs included anaemia (48.3%) and proteinuria (44.8%). SAEs were reported in 6 pts and they were not related to CS1001. irAEs occurred in 7 pts. Among the 29 pts, 7 (24%) pts had PR, mDoR was not reached. In Phase Ib, 162 pts were enrolled as of 15 Mar 2019.
Conclusions
CS1001 is well tolerated without DLT across the dose levels investigated. Evidence of anti-tumor activities was observed. Currently, 1200 mg fixed dose Q3W is being explored in various tumor types in Phase Ib, safety and efficacy results of selected Phase Ib expansion arms will be reported at the conference presentation.
Clinical trial identification
NCT03312842.
Editorial acknowledgement
Legal entity responsible for the study
CStone Pharmaceuticals (Su Zhou) Co., Ltd.
Funding
CStone Pharmaceuticals (Su Zhou) Co., Ltd.
Disclosure
J. Ding: Full / Part-time employment: CStone Pharmaceuticals. J. Wang: Full / Part-time employment: CStone Pharmaceuticals. Y. Wang: Full / Part-time employment: CStone Pharmaceuticals. H. Dai: Full / Part-time employment: CStone Pharmaceuticals. All other authors have declared no conflicts of interest.
Resources from the same session
3186 - The landscape of immuno-oncology clinical trials in China
Presenter: Dawei Wu
Session: Poster Display session 3
Resources:
Abstract
3468 - Clinical Significance of Immune-related Creatine Phosphokinase Increase Associated with Anti PD1/PD-L1 immunotherapies.
Presenter: Samia Hajem
Session: Poster Display session 3
Resources:
Abstract
3836 - Thyroid toxicity and anti-thyroid antibodies as predictive markers for patients treated with anti-PD1 checkpoint therapy
Presenter: Wim Meer
Session: Poster Display session 3
Resources:
Abstract
1343 - Treatment-related adverse events and tolerability in patients with advanced renal cell carcinoma treated with first-line combination therapy with checkpoint inhibitors
Presenter: Thura Win Htut
Session: Poster Display session 3
Resources:
Abstract
5783 - Immune-related adverse events (irAEs) with single-agent PD-1 vs PD-L1 inhibitors: a meta-analysis of 8,730 patients from clinical trials
Presenter: Guru Sonpavde
Session: Poster Display session 3
Resources:
Abstract
5422 - EULAR recommendations for the diagnosis and the management of rheumatic immune-related adverse events due to cancer immunotherapy
Presenter: Marie Kostine
Session: Poster Display session 3
Resources:
Abstract
1202 - Radiographic characteristics and poor prognostic factors of interstitial lung disease (ILD) in nivolumab-treated patients with non-small cell lung cancer (NSCLC)
Presenter: Shinichi Sasaki
Session: Poster Display session 3
Resources:
Abstract
2749 - Use of Checkpoint Inhibitors (CPI) in Allogeneic Stem Cell Transplant Recipients: An Institutional Experience and A Systemic Review of the Literature
Presenter: Chantal Saberian
Session: Poster Display session 3
Resources:
Abstract
3256 - Deep Learning Radiomics distinguishes intrapulmonary Disease from Metastases in Immunotherapy-treated Melanoma Patients
Presenter: Thi Dan Linh Nguyen-Kim
Session: Poster Display session 3
Resources:
Abstract
5031 - Sarcoidosis-Like Reaction Mimics Progression in patients treated with immune checkpoint inhibitors
Presenter: Sophie Hans
Session: Poster Display session 3
Resources:
Abstract