- Nofazinlimab in combination with lenvatinib as first-line treatment for unresectable hepatocellular carcinoma demonstrated an objective response rate of 45.0%. The median duration of response was not yet reached as of the data cutoff date (4.2 to 18.7+ months). The median progression free survival was 10.4 months.Nofazinlimab was well tolerated, with a manageable safety profile
- The U.S. FDA has granted nofazinlimab Orphan Drug Designation for the treatment of patients with hepatocellular carcinoma
SUZHOU, China, June 5, 2022 /PRNewswire/ -- CStone Pharmaceuticals ("CStone", HKEX: 2616), a leading biopharmaceutical company focused on the research, development, and commercialization of innovative immuno-oncology therapies and precision medicines, today announced that the company has published updated results from the phase 1b study of anti-PD-1 antibody nofazinlimab (CS1003) in combination with lenvatinib as first-line treatment in patients with unresectable hepatocellular carcinoma (uHCC) at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.
Dr. Jason Yang, Chief Medical Officer of CStone, said, "Preliminary results from this phase 1b study showed that nofazinlimab in combination with lenvatinib demonstrated promising and durable efficacy in Chinese patients with advanced hepatocellular carcinoma (HCC) and a well-tolerated safety profile. The Phase 3 international multi-regional registrational study of nofazinlimab plus lenvatinib for the first-line treatment of advanced HCC has already achieved the prespecified target on patient enrollment. We expect this combination therapy to provide a new treatment option for HCC patients worldwide."
CS1003-102 is a phase Ia/Ib, open-label, multi-center, dose-escalation and expansion study conducted in China. The primary objectives of Arm 5 of phase Ib was to evaluate the preliminary anti-tumor activity of nofazinlimab in combination with lenvatinib in first-line treatment of uHCC in China. The primary endpoint was objective response rate (ORR) per RECIST V1.1 by investigators.
A total of 20 patients with uHCC in Arm 5 of phase Ib study for CS1003-102 received nofazinlimab 200 mg, intravenously once every three weeks in combination with lenvatinib orally once daily (body weight ≥ 60 kg: 12 mg; < 60 kg: 8 mg) as 1L treatment. The baseline characteristics of the 20 patients were Barcelona Clinic Liver Cancer (BCLC) stage B or C, Child-Pugh class A, and ECOG PS ≤ 1.
As of August 13, 2021:
- The confirmed ORR was 45.0%, and 9 patients achieved partial response (PR).
- The median duration of response (mDOR) was not reached as of the data cutoff date (4.2 to 18.7+ months).
- The disease control rate (DCR) was 90.0%, and 9 patients had stable disease (SD) as best overall response.
- The median progression-free survival (mPFS) was 10.4 months (95% CI: 6.2, not estimable). The 6-month and 12-month progression free survival (PFS) rates were 85.0% and 48.2%, respectively.
- The median overall survival (mOS) had not been reached.
- All adverse events (AEs) were Grade 1-3.
- Grade 3 AEs attributed to nofazinlimab and/or lenvatinib occurred in 9 (45.0%) patients with the most common being gamma-glutamyltransferase increased (2/20, 10.0%). Six (6) patients experienced grade 3 nofazinlimab-related AEs, among whom, 4 patients also experienced grade 3 AEs related to lenvatinib.
- Only 2 patients discontinued treatment due to AEs.
- No deaths due to AEs, and no new safety signals were identified.
About hepatocellular carcinoma (HCC)
Liver cancer is a common malignant tumor of digestive system worldwide. According to GLOBOCAN 2020 (Global Cancer Incidence, Mortality and Prevalence) data of the International Agency for Research on Cancer (IARC), a specialized agency of the World Health Organization, global new cases of liver cancer is more than 900,000, and death cases are more than 830,000 per year. The number of death cases is close to the number of new cases. Liver cancer is the second leading cause of cancer- related death and its incidence is increasing globally. HCC is the most common form of liver cancer and accounts for ~90% of cases. Systemic antitumor therapy plays an important role in the treatment of advanced HCC. Despite the expanding implementation of surgical and locoregional therapies worldwide, estimates suggest that ~50–60% of patients with HCC will ultimately be treated with systemic therapies2. A median survival for symptomatic advanced-stage HCC cases treated with systemic therapies is ~1–1.5 years2. Poor prognosis of HCC is attributed primarily to tumor presentation at an advanced stage when there is no effective treatment to achieve the long-term survival of patients.
About nofazinlimab (CS1003）
Nofazinlimab is a humanized recombinant IgG4 monoclonal antibody targeting human programmed cell death protein 1 (PD-1) being developed in solid tumors. Nofazinlimab shows comparable high binding affinities to the PD-1 of humans, cynomolgus monkey, and mouse, and can block the interaction of PD-1 with its ligands PD-L1 and PD-L2.
The U.S. FDA has granted nofazinlimab Orphan Drug Designation (ODD) in July 2020 for the treatment of patients with HCC.
CStone formed a strategic collaboration agreement with EQRx, under which EQRx licensed the exclusive rights to two immuno-oncology assets, sugemalimab and nofazinlimab, for development and commercialization outside of Greater China. CStone retains rights to nofazinlimab in Greater China, where it can continue to pursue development as a monotherapy or as part of its combination strategy for this drug.
About the CS1003-305 study
CS1003-305 is an international, multi-center, double-blind, randomized, phase 3 registrational clinical trial to evaluate the efficacy and safety of nofazilimab in combination with lenvatinib compared with placebo in combination with lenvatinib in subjects with no prior systemic treatment and with unresectable advanced HCC. The trial is conducted in 74 study sites globally including China, US, Spain, Italy, and Poland. The primary endpoints are overall survival (OS) and PFS. Dr. Jia Fan, academician of Chinese Academy of Sciences (CAS) and president of Zhongshan Hospital affiliated to Fudan University, is the global principal investigator for this trial. In March 2022, this study successfully reached its prespecified enrollment target.
CStone (HKEX: 2616) is a biopharmaceutical company focused on researching, 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, CStone has received eight NDA approvals for four drugs. Multiple late-stage drug candidates are now under pivotal clinical trials or registration. CStone's vision is to become globally recognized as a world-renowned biopharmaceutical company by bringing innovative oncology therapies to cancer patients worldwide.
For more information about CStone, please visit www.cstonepharma.com.
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 Shen L et al, ESMO Congress 2020, Abstract 987P, A Phase 1b study of the PD-1 antagonist CS1003 plus lenvatinib (LEN) in Chinese patients (pts) with the first-line (1L) unresectable hepatocellular carcinoma (uHCC).
 Llovet JM et al, Nat Rev Clin Oncol. 2022 Mar;19(3):151-172. Immunotherapies for hepatocellular carcinoma
 Llovet JM et al, Nat Rev Dis Primers. 2021 Jan 21;7(1):6. Hepatocellular carcinoma.
 Ahn JC et al, Hepatology. 2021 Jan;73(1):422-436. Detection of Circulating Tumor Cells and Their Implications as a Biomarker for Diagnosis, Prognostication, and Therapeutic Monitoring in Hepatocellular Carcinoma