CStone Pharmaceuticals has announced that two pivotal phase II studies exploring the efficacy and safety of CS1001 in patients with natural killer cell/T-cell lymphoma (CS1001-201) and classical Hodgkin's lymphoma (CS1001-202) have been initiated, and have respectively enrolled and dosed the first patient. CS1001 is China’s first fully human, full-length, IgG4 based anti-PD-L1 monoclonal antibody independently developed by CStone.

“These two pivotal phase II studies give us great confidence in the potential accelerated commercialization of CS1001,” said Dr. Frank Jiang, chief executive officer of CStone. “We believe that CS1001 will become one of the first locally-developed anti-PD-L1 cancer drugs launched in China. Meanwhile, our experience in the clinical development of CS1001 will lay a solid foundation for the development of subsequent products in the pipeline.”

The two pivotal Phase II studies, CS1001-201 and CS1001-202, will take the objective response rate (ORR) as the primary endpoint to measure the drug’s efficacy, and will also examine the drug’s safety, pharmacokinetics, and immunogenicity. Both CS1001-201 and CS1001-202 are open-label, single-arm studies that are conducted simultaneously at multiple clinical study centers across the country, including the Sun Yat-sen University Cancer Center and the Beijing Cancer Hospital. The results of the two studies will be used to support the registration application for the drug.

“Natural killer cell/T-cell lymphoma and classical Hodgkin's lymphoma are relatively rare malignant cancers that affect the blood system, and most patients are young and middle-aged. Patients who fail the current standard treatment normally have a very short survival period. As such, there are significant unmet medical needs in these diseases,” further commented by Dr. Jason Yang, chief medical officer of CStone. “According to recent preclinical and clinical studies, targeting the PD-1/PD-L1 pathways is the most effective way to treat these hematological malignancies. The clinical development of CS1001 and its future registration will provide an effective therapy and an additional option to patients.”

CS1001 is an investigational monoclonal antibody directed against PD-L1 being developed by CStone Pharmaceuticals. Authorized by the U.S.-based Ligand Corporation, CS1001 is a monoclonal antibody developed by the OMT transgenic animal platform, which can generate fully human antibodies in one step. As a fully human, full-length anti-PD-L1 monoclonal antibody, CS1001 mirrors natural G-type immune globulin 4 (IgG4) human antibody, which could reduce the risk of immunogenicity and potential toxicities in patients, a unique advantage over similar drugs.

A first-in-human phase I study (CS1001-101) has been conducted by CStone Pharmaceuticals since October 2017 to evaluate the safety, tolerability, pharmacokinetics and anti-tumor activity of CS1001 in patients with advanced tumors in China. The phase Ia (dose escalation) part was completed in May 2018, and the phase Ib (dose expansion) part has recently started patient recruitment. In parallel, several pivotal studies are underway, including tumor types with high incidence and prevalence rates in China.

Programmed cell death ligand-1 (PD-L1) is a 40 kDa type I transmembrane protein. Under normal physiological conditions, the immune system responds to antigens in the lymph nodes or spleen by promoting the proliferation of antigen specific T cells. The combination of programmed cell death protein-1 (PD-1) and PD-L1 can transduce inhibitory signals to reduce the proliferation of T cells and control an overreaction by the immune system, enabling the body to resume its natural immune balance after the pathogens are removed. However, within the tumor microenvironment, cancer cells can up-regulate PD-L1 expression levels, strongly inhibiting the body's natural antitumor immune response and allowing tumor cells to "escape" the recognition and attack by the immune system. Currently, monoclonal antibody drugs targeting PD-1 or PD-L1 have been developed and approved globally. In China, there are more anti-PD-1 targeting monoclonal drugs being developed than anti-PD-L1. As such, the clinical study of CS1001, the first fully human, full-length anti-PD-L1 monoclonal antibody in China, has significant scientific and therapeutic value.

CStone Pharmaceuticals is a clinical stage biopharmaceutical company devoted to the development of innovative drugs. With a broad pipeline, the company engages in the development of cancer therapeutics with a special focus on immuno-oncology based combination therapies.