Suzhou, China, January 15th, 2022 - CStone Pharmaceuticals (“CStone”, HKEX: 2616), a leading biopharmaceutical company focused on research, development, and commercialization of innovative immuno-oncology therapies and precision medicines, today announced that results of the GEMSTONE-302 study, a randomized double-blind registrational clinical study for sugemalimab as the first-line treatment of stage IV non-small cell lung cancer (NSCLC) were published in the world-leading oncology journal The Lancet Oncology. Sugemalimab plus chemotherapy demonstrates statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with placebo plus chemotherapy. The publication in The Lancet Oncology shows the great academic value and clinical potential of sugemalimab. Based on the results of the GEMSTONE-302 study, sugemalimab has recently been approved in China in combination with chemotherapy as the first-line treatment of patients with metastatic NSCLC. The GEMSTONE-302 is the world’s first randomized, double-blind, phase 3 trial of anti-PD-L1 monoclonal antibody plus chemotherapy as first-line treatment for stage IV squamous or non-squamous NSCLC, and the study was conducted in 35 hospitals and academic research centers in China. The leading Principal Investigator of the GEMSTONE-302 study is Professor Caicun Zhou, Director of the Department of Oncology, Shanghai Pulmonary Hospital.

source: The Lancet Oncology      https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00650-1/fulltext

The GEMSTONE-302 study was designed to evaluate the efficacy and safety of sugemalimab plus chemotherapy compared with placebo plus chemotherapy as first-line treatment of patients with stage IV NSCLC.

In 2020, at the pre-planned interim analysis of PFS (median follow-up of 8.6 months), the GEMSTONE-302 study met its primary endpoint with significantly prolonged PFS in the sugemalimab group versus the placebo group. In 2021, with a median follow-up of 17.8 months, the final analysis of PFS showed that sugemalimab plus chemotherapy continued to enhance the benefit in the primary efficacy endpoint of PFS. The hazard ratio (HR) (95% CI) of investigator-assessed PFS was 0.48 (0.39, 0.60). The median PFS was 9.0 months for sugemalimab plus chemotherapy and 4.9 months for placebo plus chemotherapy. Subgroup analyses of PFS showed clinical benefits across different histological types (squamous or non-squamous) and different PD-L1 expression levels (≥1% or <1%). Sugemalimab plus chemotherapy was well-tolerated, with no new safety signals observed. Meanwhile, sugemalimab showed an encouraging trend for overall survival (OS) in preliminary analysis. The trial is being continued and formal statistical testing for OS is to be performed.

Professor Caicun Zhou, Principal Investigator of the GEMSTONE-302 study, Corresponding Author of the paper, and Director of the Department of Oncology, Shanghai Pulmonary Hospital, said, “We are very glad that the results of the GEMSTONE-302 study were invited for publication in The Lancet Oncology, fully demonstrating the international academic community’s recognition of its innovative and rational study design, high quality research and promising results. The study results of sugemalimab marked a breakthrough in the use of anti-PD-L1 immunotherapy plus chemotherapy. Our findings suggest sugemalimab could be a new safe and effective treatment option for non-squamous NSCLC patients of an anti PD-L1 immunotherapy with carboplatin and pemetrexed. It should also be noted that this study provides the only anti-PD-L1 immunotherapy plus chemotherapy option for squamous NSCLC patients worldwide.”

Dr. Jason Yang, Chief Medical Officer of CStone, said, “The publication of the GEMSTONE-302 study in The Lancet Oncology demonstrated the high recognition of the academic value of sugemalimab by the world-leading academic journal. Recently, sugemalimab has been approved in China for the first-line treatment of metastatic NSCLC. Meanwhile, we’ve achieved milestones in advancing multiple registrational studies in lymphoma, gastric cancer, and esophageal squamous cell carcinoma, and we expect sugemalimab to benefit more patients.”

In addition, the National Medical Products Administration (NMPA) of China accepted the new drug application (NDA) for sugemalimab in the treatment of patients with locally advanced (stage III) NSCLC in September 2021, and the review is ongoing. With the positive data of sugemalimab in locally advanced (stage III) and metastatic (stage IV) NSCLC, it has the potential to become the world’s first PD-(L)1 monoclonal antibody to cover stage III and stage IV NSCLC in all-comer settings.

***

About Sugemalimab

Sugemalimab is an investigational anti-PD-L1 monoclonal antibody discovered by CStone. Authorized by the U.S.-based Ligand Corporation, sugemalimab is developed by the OmniRat^® transgenic animal platform, which can generate fully human antibodies in one stop. As a fully human, full-length anti-PD-L1 monoclonal antibody, sugemalimab mirrors the natural G-type immunoglobulin 4 (IgG4) human antibody, which reduces the risk of immunogenicity and potential toxicities in patients, a unique advantage over similar drugs.

Currently, the NMPA of China has approved sugemalimab (Cejemly^®) in combination with pemetrexed and carboplatin as first-line treatment of patients with metastatic non-squamous NSCLC, with no EGFR or ALK genomic tumor aberrations; and in combination with paclitaxel and carboplatin as first-line treatment of patients with metastatic squamous NSCLC. sugemalimab is being investigated in a number of ongoing clinical trials, including one Phase 2 registrational study for lymphoma and four Phase 3 registrational studies in stage III NSCLC, stage IV NSCLC, gastric cancer, and esophageal cancer, respectively.

About the GEMSTONE-302 study

The GEMSTONE-302 study (ClinicalTrials.gov registration number: NCT03789604; drug clinical trial registration number: CTR20181452) is a randomized, double-blind Phase 3 study, designed to evaluate the efficacy and safety of anti-PD-L1 monoclonal antibody sugemalimab in combination with chemotherapy as the first-line treatment in treatment-naïve patients with stage IV NSCLC vs. placebo in combination with chemotherapy. The primary endpoint of the study was investigator-assessed PFS. Secondary endpoints included overall survival, BICR-assessed PFS and safety, etc.

In August 2020, the GEMSTONE-302 study met its primary endpoint of significantly prolonged PFS, with the risk of disease progression or death reduced by 50% with sugemalimab plus chemotherapy compared to placebo plus chemotherapy, as assessed by iDMC at the pre-planned interim analysis. Study data were presented in a Proffered Paper Oral Presentation (Late-Breaking Abstract) at the ESMO Asia 2020.

In July 2021, the final analysis of PFS from the GEMSTONE-302 study showed that sugemalimab in combination with chemotherapy demonstrated continued improvement in PFS and the risk of disease progression or death was reduced by 52%, together with a trend of overall survival benefits. Data were accepted as Late-Breaking Abstract and orally presented in the IASLC 2021 World Conference on Lung Cancer.

About the GEMSTONE-301 study

The GEMSTONE-301 study is (clinicaltrials.gov registration number: NCT03728556; drug clinical trial registration number: CTR20181429) is a multicenter, randomized, double-blind Phase 3 clinical trial, designed to evaluate the efficacy and safety of sugemalimab as consolidation therapy in patients with unresectable stage III NSCLC without disease progression after concurrent or sequential chemoradiotherapy. The trial's primary endpoint was PFS as assessed by BICR according to RECIST v1.1; the secondary endpoints included overall survival, PFS as assessed by investigators and safety, etc.

In May 2021, the GEMSTONE-301 study met its primary endpoint at a pre-planned interim analysis reviewed by the iDMC. The findings showed that sugemalimab brought statistically significant and clinically meaningful improvement in the BICR assessed PFS. Investigator-assessed PFS showed consistent results as those of the primary endpoint. Sugemalimab was well-tolerated with no new safety signals. Subgroup analyses demonstrated that sugemalimab was associated with clinical benefit regardless of whether patients received concurrent or sequential chemoradiotherapy prior to sugemalimab. The data were accepted as Late-Breaking Abstract (LBA) and orally presented at the 2021 ESMO Annual Meeting.

In September 2021, the NMPA of China accepted the NDA for sugemalimab as a consolidation therapy in patients with unresectable stage III NSCLC without disease progression after concurrent or sequential chemoradiotherapy.

About CStone

CStone Pharmaceuticals (HKEX: 2616) is a leading 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 therapies and precision medicines. Currently, CStone has received five drug approvals in Greater China, including three in Mainland China, one in Hong Kong, and one in Taiwan. 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.

Forward-looking statement

The forward-looking statements made in this article only relate to events or information as of the date when the statements are made in this article. Except as required by law, we undertake no obligation to update or publicly revise any forward-looking statements, whether as a result of new information, future events or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. All statements in this article are made on the date of publication of this article and may change due to future developments.