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
4868 - Evaluation of markers associated with efficacy of abiraterone acetate plus prednisone (AAP) in patients (pts) with castration-sensitive prostate cancer (mCSPC) from the LATITUDE study
Presenter: Kim Chi
Session: Poster Display session 3
Resources:
Abstract
4837 - LRP2, a potential new biomarker for Chinese younger aged intrahepatic cholangiocarcinoma patients
Presenter: Xiaoliang Shi
Session: Poster Display session 3
Resources:
Abstract
1286 - Reanalysis of the efficacy of molecular targeted agents (MTAs) given in the randomized trial SHIVA01 according to the ESMO ESCAT scale of actionability
Presenter: Aurelie Moreira
Session: Poster Display session 3
Resources:
Abstract
2736 - Comparison of Platforms for Determining Tumor Mutational Burden (TMB) From Blood Samples in Patients With Non-Small Cell Lung Cancer (NSCLC)
Presenter: Jonathan Baden
Session: Poster Display session 3
Resources:
Abstract
5045 - Comprehensive Pan-Cancer analysis of somatic mutations in drug transporters to reveal acquired and intrinsic drug resistance in 3149 metastatic cancer patients
Presenter: Sander Bins
Session: Poster Display session 3
Resources:
Abstract
4577 - Pan-Cancer Genomic Landscape of the Cyclin D1/FGF3,4,19 (11q13) Amplicon Including Associations with HPV Status, and ESR1 and AR Alterations
Presenter: Jennifer Johnson
Session: Poster Display session 3
Resources:
Abstract
5366 - Co-occurrence of NTRK fusions with other genomic biomarkers in cancer patients
Presenter: Xiaolong Jiao
Session: Poster Display session 3
Resources:
Abstract
4084 - Prospective comparative study of next-generation sequencing on fine needle aspirations versus core needle biopsies in cancer patients included in SHIVA02 trial
Presenter: Julien Masliah-Planchon
Session: Poster Display session 3
Resources:
Abstract
6017 - First national External Quality Assessement for the interpretation of somatic variants: assessment of 25 variants in colorectal, lung, ovarian cancers and melanoma in France
Presenter: Etienne Rouleau
Session: Poster Display session 3
Resources:
Abstract
2283 - Prospective testing of circulating tumor DNA in metastatic breast cancer facilitates clinical trial enrollment and precision oncology
Presenter: Andjelija Bujak
Session: Poster Display session 3
Resources:
Abstract