• CS1003-101 study : CS1003 was evaluated for the treatment of advanced solid tumors. The average plasma concentration (Cavg,ss) at steady-state were found to be similar between the 200 mg Q3W and 400 mg Q6W dosing regimens. CS1003 demonstrated potent anti-tumor activity and a benign safety profile, with an objective response rate (ORR) of 24.1% and 32.3% for the 200 mg Q3W and 400 mgQ6W dosing regimen, respectively
• CS1003-102 study: CS1003 was evaluated in combination with lenvatinib (LEN) as a first-line treatment for Chinese patients with unresectable hepatocellular carcinoma (uHCC). This combination demonstrated robust efficacy and was well tolerated, with an ORR of 40%

(Suzhou, China, September 25, 2020) CStone Pharmaceuticals (Suzhou) Co., Ltd. (“CStone", HKSE: 2616) presented the results from two Phase 1 studies of CS1003 at the 2020 ESMO Meeting held from September 19th to September 21st, 2020. CS1003-101 study (Poster ID 1057P) was designed to evaluate the safety, PK, immunogenicity and preliminary anti-tumor activity of CS1003 in patients with advanced cancer, and CS1003-102 (Poster ID: 987P) was designed to evaluate CS1003 in combination with lenvatinib (LEN) as a first-line (1L) treatment for Chinese patients with unresectable hepatocellular carcinoma (uHCC). In both studies, CS1003, used either as monotherapy or in combination with standard of care (SoC), was safe and well tolerated, and demonstrated promising anti-tumor activity, supporting future clinical development of this molecule as an immune-oncology backbone agent.

CS1003 is a full-length, humanized immunoglobulin G4 (IgG4) monoclonal antibody against PD-1 developed by CStone Pharmaceuticals. Unlike other anti-PD-1 antibodies, CS1003 has comparable binding affinity against both human and mouse PD-1, which allows rapid evaluation of anti-tumor effect in syneneic mouse tumor models, including the combination with lenvatinib described herein.

About CS1003-101(NCT03475251)

The phase 1b part of the first-in-human study of CS1003 (NCT 03475251) aimed to evaluate the efficacy, safety and pharmacokinetics of two dosing schedules of CS1003, at 200 mg Q3W and at 400 mg Q6W. The primary endpoint was objective response rate (ORR) per RECIST V1.1 by investigators, and secondary endpoints included progression-free survival (PFS), disease control rate (DCR), duration of response (DOR), overall survival (OS), safety, tolerability, pharmacokinetics, and immunogenicity.

In patients with advanced solid tumors, the average plasma concentration at steady state ( Cavg,ss ) of 400mg Q6W was comparable to that of 200 mg Q3W. Both dosing regimens are well tolerated and showed promising antitumor activity with an ORR of above 20%.

• As of July 15th, 2020, Cohort A (200 mg Q3W) enrolled 29 patients and Cohort B (400 mg Q6W) enrolled 31 patients
• 15 patients from Cohort A and and 4 patients from Cohort B were included in the steady-state PK analysis. The average plasma concentration ( Cavg, ss) of the two dosing regimens were comparable to each other
• A total of 29 patients from cohort A and 31 patients from cohort B were included in the Efficacy Analysis Set. The ORRs in cohort A and in Cohort B were 24.1% and 32.3%, respectively (confirmed ORRs in Cohort A and in Cohort B were 20.7% and 25.8% respectively); the median DoR in both Cohort A and Cohort B had not been reached
• A total of 29 patients from cohort A and 31 patients from cohort B were included in the Safety Analysis Set. At least one treatment-emergent AE (TEAE) was reported in 96.6% and 96.8% of the patients from Cohort A and B, respectively. Most treatment related TRAEs were of Grade 1-2; the incidence of Grade 3-4 treatment related TEAEs in Cohort A and Cohort B were 0% and 9.7%, respectively; no treatment-related deaths were observed; and the incidence of immune-related AEs were comparable between Cohort A (34.5%) and Cohort B ( 32.3%)
• CS 1003 dosing regimen at 400 mg Q6W offers a more flexible and convenient dosing option

Waterfall of Maxium Target Lesion Shrinkage per RECIST v1.1 (Efficacy Analysis Set)

About CS1003-102(NCT03809767）

CS1003-102(NCT03809767) is a multi-center, open-label phase I dose escalation, and indication expansion study conducted in China , Arm 5 of Phase Ib part of which aimed to evaluate the safety and efficacy of CS1003 in combination with lenvatinib (LEN) as a first-line treatment for Chinese patients with unresectable HCC (uHCC). The primary endpoint was objective response rate (ORR) per RECIST V1.1 by investigators, and secondary endpoints included progression-free survival (PFS), disease control rate (DCR), duration of response (DOR) , overall survival (OS), safety and tolerability, pharmacokinetics, and immunogenicity.

As of June 22nd, 2020, a total of 20 patients were enrolled and received treatment. The majority of patients were male (90%), had a ECOG score of 1 (75%), had BCLC stage C HCC (90%), and had HBV infection (65%)

CS1003 in combination with lenvatinib (LEN) as a first-line treatment of Chinese patients with unresectable hepatocellular carcinoma (uHCC) demonstrated promising efficacy and was well tolerated:

• A total of 20 patients were included for efficacy analysis set, of which 6 patients achieved a confirmed partial response (PR) , and 2 other patients had their PR confirmed after the data cut-off. The ORR was 40% (8/20)
• Median follow-up duration was 6.2 months, and median PFS was 8.4 months. By the data cut-off date, median OS and DoR had not been reached
• A total of 20 patients were included in the safety analysis set. The most common treatment related TEAEs of any grade were elevated bilirubin , urine protein present and proteinuria. Five patients each had a Grade 3 treatment related TEAE, including hypertension, elevated conjugated bilirubin, diarrhea, diabetes, and hypophosphatemia. No patients had Grade 4/5 treatment related TEAE.

Time on Treatment, Individual Best Response (Efficacy Analysis Set）

Dr. Archie Tse, Chief Translational Meidicne Officer of CStone, said, “We are very pleased to see the excellent efficacy and safety demonstrated by CS1003 monotherapy alone or in combination with standard treatment so far. CS1003 is a monoclonal antibody with high-affinity to disrupt the interaction of PD-1 with its ligands. CS1003 has demonstrated good safety and anti-tumor activity in patients with advanced solid tumors. The 400mg Q6W dosing regimen offers a more flexible and convenient dosing option for patients. In addition, as a novel anti-PD-1, CS1003 in combination with lenvatinib has resulted in an ORR of 40%, indicating a potential clinical advantage for treating advanced uHCC. All of these preliminary results support further development of CS1003 as an immune-oncology backbone agent”.

About CS1003

CS1003 is a humanized recombinant IgG4 monoclonal antibody targeting human programmed cell death protein 1 (PD-1) being developed for immunotherapy of various tumors. Compared to most of the monoclonal antibodies that bind human and monkey PD-1(either already approved or in clinical stage) , CS1003 demonstrates comparable high binding affinities across species against human, cynomolgus moneky and mouse PD-1, and is developed to disrupt the interaction of PD-1 with its liagands PD-L1 and PD-L2 . CS1003 is also unique in that it can simultaneously recognize human and mouse PD-1, which allows fast pre-clinical proof of concept for CS1003 in combination with novel targeted therapies using syngeneic mouse tumor models.

About CStone

CStone Pharmaceuticals (HKEX:2616) is a biopharmaceutical company focused on developing and commercializing innovative immuno-oncology and precision medicines to address the unmet medical needs of cancer patients in China and worldwide. Established in 2015, CStone has assembled a world-class management team with extensive experience in innovative drug development, clinical research, and commercialization. The company has built an oncology-focused pipeline of 15 drug candidates with a strategic emphasis on immuno-oncology combination therapies. Currently, five late-stage candidates are at or near pivotal trials. With an experienced team, a rich pipeline, a robust clinical development-driven business model and substantial funding, CStone’s vision is to become globally recognized as a leading Chinese biopharmaceutical company by bringing innovative oncology therapies to cancer patients worldwide.

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