On August 7, 2020 Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) reported CStone Pharmaceuticals ("CStone", HKEX: 2616) that its OmniAb-derived anti-PD-L1 mAb CS1001 combined with platinum-based chemotherapy met its pre-specified primary endpoint, as assessed by the independent Data Monitoring Committee at the planned interim analysis of CS1001-302, a randomized, double-blind Phase 3 clinical trial for the first-line treatment of stage IV squamous and non-squamous NSCLC patients (Press release, Ligand, AUG 7, 2020, View Source [SID1234563162]).

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Key data highlights include:

In the overall population containing both squamous and non-squamous NSCLC patients, investigator-assessed progression free survival (PFS) HR (95% CI) was 0.50 (0.39, 0.64), p<0.0001. The median PFS was 7.8 months vs. 4.9 months in CS1001 combined with chemotherapy and placebo combined with chemotherapy, respectively.
Subgroup analyses showed clinical benefit across histology subtypes and PD-L1 expression levels.
Blinded independent central review (BICR)-assessed PFS as a secondary endpoint was consistent with the investigator-assessed PFS. Other secondary endpoints also supported the primary endpoint result.
CS1001 in combination with chemotherapy was well tolerated, with no new safety signal detected.
"This is an outstanding clinical report by CStone and also the most substantial, pivotal-stage data to be reported to date for an OmniAb-derived antibody," said John Higgins, Chief Executive Officer of Ligand. "These results, coupled with data recently announced by Genentech relating to their OmniAb-derived anti-TIGIT program, are ushering in what we believe will be a period of major data, breakthroughs and late-stage developments for new potential OmniAb-derived human therapeutics. Our OmniAb platform continues to be a valuable tool to efficiently discover high-quality fully human antibody therapeutics. We congratulate CStone on this remarkable achievement and contribution to improving potential treatment options for lung cancer."

Dr. Frank Jiang, Chairman and CEO of CStone, said, "Currently, there is no anti-PD-L1 monoclonal antibody approved for NSCLC in China. CS1001 is the first anti-PD-L1 monoclonal antibody combined with chemotherapy to demonstrate significant improvement in PFS in Chinese NSCLC patients. It has the potential of becoming the world’s first anti-PD-L1 monoclonal antibody that can be combined with chemotherapy as the first-line treatment of both squamous and non-squamous NSCLC patients. This further strengthens our confidence in the development of CS1001 and greatly expediate CStone’s commercialization progress."

Dr. Jason Yang, Chief Medical Officer of CStone, said, "Compared with published results of other anti-PD-1/PD-L1 monoclonal antibodies in combination with chemotherapy in first-line NSCLC trials, the CS1001-302 study, with an innovative design, is the first phase 3 clinical study in China for the first-line treatment of both squamous and non-squamous NSCLC subtypes. We will continue to make every effort to promote and more extensively evaluate the potential clinical benefit of this product in patients with hematological malignancies, stage III NSCLC, advanced gastric cancer, liver cancer and esophageal cancer."

About OmniAb

OmniAb is a three-species transgenic-animal platform consisting of five different technologies used for producing mono- and bispecific human therapeutic antibodies. OmniRat animals comprise the industry’s first human monoclonal antibody technology based on rats. Because they have a complete immune system with a diverse antibody repertoire, OmniRat animals generate antibodies with human idiotypes as effectively as wild-type animals make rat antibodies. OmniMouse is a transgenic mouse that complements OmniRat and expands epitope coverage. OmniFlic is an engineered rat with a fixed light chain for development of bispecific, fully human antibodies. OmniChicken animals comprise the industry’s first human monoclonal antibody technology based on chickens. The OmniClic chicken is specifically developed to facilitate the generation of bispecific antibodies and retains the ability to generate diverse, high quality affinity matured antibodies. All five types of OmniAb therapeutic human antibody platform, OmniRat, OmniFlic, OmniMouse, OmniChicken and OmniClic, use patented technology, have broad freedom to operate, produce highly diversified, fully human antibody repertoires optimized in vivo for immunogenicity, manufacturability, and therapeutic efficacy, and deliver fully human antibodies with high affinity, specificity, expression, solubility and stability – Naturally Optimized Human Antibodies.

About Non-Small Cell Lung Cancer and China

In contrast to most Western countries, where lung cancer death rates are decreasing, lung cancer incidence rates are still increasing in China. There were approximately 770,000 new cases of lung cancer in China in 2018, and it is the leading cause of cancer-related death in both men and women, with approximately 690,500 deaths in China in 2018. Non-small cell lung cancer comprises the most common form of lung cancer in China.

CS1001-302 Study

CS1001-302 is a multicenter, randomized, double-blind Phase 3 clinical trial (CS1001-302; clinicaltrials.gov registration number: NCT03789604; drug clinical trial registration number: CTR20181452), designed to evaluate the efficacy and safety of CS1001 in combination with platinum-containing chemotherapy versus placebo in combination with platinum-containing chemotherapy in first-line naïve patients with stage IV NSCLC. The primary endpoint of the trial was PFS as assessed by the investigators; the secondary endpoints include overall survival, PFS and the safety profile as assessed by BICR committee.

About CS1001

CS1001 is an investigational anti-PD-L1 monoclonal antibody discovered by CStone using Ligand Pharmaceuticals’ OmniRat transgenic animal platform, which can generate fully human antibodies. As a fully human, full-length anti-PD-L1 monoclonal antibody, CS1001 mirrors the natural G-type immunoglobulin 4 (IgG4) human antibody, which can reduce the risk of immunogenicity and potential toxicities in patients, representing a unique advantage over similar drugs. CS1001 has completed a Phase 1 dose-escalation study in China. During Phase 1a and Phase 1b of the study, CS1001 showed good antitumor activity and tolerability in multiple tumor types. Currently, CS1001 is being investigated in a number of ongoing clinical trials. In addition to a Phase 1 bridging study in the U.S., the clinical program in China includes one multi-arm Phase 1b study for several tumor types, two Phase 2 registrational studies for lymphoma, and four Phase 3 registrational studies, respectively, for stage III/IV NSCLC, gastric cancer, and esophageal cancer.