Sugemalimab is the world’s first anti-PD-1/PD-L1 monoclonal antibody to significantly improve progression-free survival (PFS) in patients with stage III non-small cell lung cancer (NSCLC) without disease progression after concurrent or sequential chemoradiotherapy
The data showed that sugemalimab demonstrated a statistically significant and clinically meaningful improvement in the Blinded Independent Central Review (BICR) assessed PFS. The risk of disease progression or death was reduced by 36%, together with encouraging overall survival (OS). The risk of death was lowered by 56%. Subgroup analyses demonstrated clinical benefits regardless of whether patients received concurrent or sequential chemoradiotherapy prior to sugemalimab
The National Medical Products Administration (NMPA) of China has accepted the new drug application (NDA) for sugemalimab in patients with unresectable stage III NSCLC

SUZHOU, China, Sept. 17, 2021 /PRNewswire/ — CStone Pharmaceuticals (“CStone”, HKEX: 2616), a leading biopharmaceutical company focused on researching, developing and commercializing innovative immuno-oncology therapies and precision medicines, today announced that data from the GEMSTONE-301 study, a registrational Phase 3 study of sugemalimab for the treatment of patients with stage III NSCLC, was accepted as a late-breaking abstract (LBA) at the European Society for Medical Oncology (ESMO) Congress 2021, and unveiled via a mini oral presentation at the Congress.

Presentation session: Non-metastatic NSCLC and other thoracic malignancies
Date: 23:50-23:55 (Beijing time), September 18th, 2021
Format: Mini Oral Presentation
Title: GEMSTONE-301: A randomized, double-blind, placebo-controlled, phase 3 study of sugemalimab in patients with unresectable stage III non-small cell lung cancer (NSCLC) who had not progressed after concurrent or sequential chemoradiotherapy (CRT)
Presentation number: LBA 43
Principal Investigator & presenter: Professor Yi-Long Wu, Guangdong Provincial People’s Hospital

The GEMSTONE-301 study is designed to evaluate the efficacy and safety of sugemalimab as a consolidation therapy in patients with unresectable stage III NSCLC without disease progression after concurrent or sequential chemoradiotherapy. The GEMSTONE-301 study has an innovative study design that enrolled patients with either concurrent or sequential chemoradiotherapy to better reflect real-world clinical practice and cover a broad NSCLC patient population. In May 2021, the GEMSTONE-301 study met its primary endpoint at the planned interim analyses reviewed by the iDMC. The data showed that sugemalimab as a consolidation therapy brought statistically significant and clinically meaningful improvement in PFS as assessed by BICR. The detailed results of sugemalimab versus placebo as a consolidation therapy reported at ESMO 2021 are displayed as follows:

BICR-assessed PFS was 9.0 months vs 5.8 months, stratified HR=0.64 (95% CI:0.48, 0.85), p-value=0.0026
Clinical benefits were observed in patients who received either concurrent or sequential chemoradiotherapy prior to sugemalimab:
For patients who received prior concurrent chemoradiotherapy: The median PFS was 10.5 months vs 6.4 months, HR=0.66
For patients who received prior sequential chemoradiotherapy: The median PFS was 8.1 months vs 4.1 months, HR=0.59
The median OS was not reached vs 24.1 months, stratified HR=0.44
Sugemalimab had a well-tolerated safety profile; no new safety signals were observed.
Grade≥3 treatment-emergent adverse events (TEAEs) occurred in 24.3% and 23.8% of patients in the two groups, respectively

“There is no effective therapy available for patients with stage III NSCLC without disease progression after sequential chemoradiotherapy,” said Professor Yi-Long Wu of Guangdong Provincial People’s Hospital, the Leading Principal Investigator on the GEMSTONE-301 study. “The data from GEMSTONE-301 showed that sugemalimab as a consolidation therapy brought statistically significant and clinically meaningful improvement in the PFS. Clinical benefits were observed in patients receiving either concurrent or sequential chemoradiotherapy prior to sugemalimab, together with a well-tolerated safety profile. With the successful data in GEMSTONE-301, sugemalimab will be well positioned to address the urgent medical needs of this patient population.”

“We are very glad that the GEMSTONE-301 study has been accepted for a late-breaking abstract (LBA) at the ESMO Congress 2021. We are so proud that these positive data have attracted extensive attention worldwide and stimulated lively discussions in the international congress,” said Dr. Jason Yang, Chief Medical Officer of CStone. “CStone is always committed to addressing unmet medical needs, and, with the GEMSTONE-301 study, we are supporting the multidisciplinary team (MDT) cooperation and bolstering medical capabilities for the diagnosis and treatment of stage III lung cancer in China. Based on the positive data in patients with locally advanced (stage III) and metastatic (stage IV) NSCLC, sugemalimab has the potential to become the world’s first anti-PD(L)1 monoclonal antibody approved for the treatment of all-comer patients from both stage III and stage IV NSCLC. Meanwhile, we will continue to advance the registrational clinical study of sugemalimab in esophageal squamous cell carcinoma, gastric cancer, and relapsed /refractory extranodal natural killer/T-cell lymphoma to benefit more cancer patients.”

The NMPA of China has accepted the NDA for sugemalimab in the treatment of patients with unresectable stage III NSCLC in September 2021. The NDA for sugemalimab in patients with metastatic (stage IV) NSCLC was accepted by the NMPA last year and is currently under review.

CStone is working closely with Pfizer to advance the commercialization of sugemalimab in Mainland China. Outside of Greater China, CStone will continue to work closely with EQRx on regulatory discussions on the two indications of stage III and stage IV NSCLC in multiple countries and regions.

About NSCLC

In recent years, China has had rising lung cancer incidence. According to the latest estimates on the global burden of cancer released by International Agency for Research on Cancer (IARC), in 2020, an estimated 0.82 million new lung cancer cases and 0.71 million new lung cancer deaths occurred in China. Among all Chinese cancer patients, lung cancer is the leading cause of cancer-related deaths. NSCLC is the most common type of lung cancer.

About Sugemalimab (anti-PD-L1 antibody)

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, sugemalimab is being investigated in a number of ongoing clinical trials, including one Phase 2 registration study for lymphoma (CS1001-201) and four Phase 3 registrational studies in stage III NSCLC, stage IV NSCLC, gastric cancer, and esophageal cancer, respectively.

CS1001-201 is a single-arm, multicenter, Phase 2 pivotal study designed to evaluate the efficacy and safety of sugemalimab as monotherapy for the treatment of adult patients with relapsed or refractory extranodal natural killer/T-cell lymphoma (R/R ENKTL). Based on the encouraging preliminary efficacy results, sugemalimab was granted Orphan Drug Designation for the treatment of T-cell lymphoma and Breakthrough Therapy Designation for the treatment of R/R ENKTL by the U.S. Food and Drug Administration. It has also been granted Breakthrough Therapy Designation by the National Medical Products Administration of China. The proposed indication is R/R ENKTL.

CStone formed a strategic collaboration agreement with Pfizer that includes the development and commercialization of sugemalimab in mainland China, and a framework to bring additional oncology assets to the Greater China market. CStone subsequently formed a strategic collaboration agreement with EQRx, under which EQRx licensed the exclusive rights to two key late-stage immuno-oncology assets, sugemalimab and CS1003 (anti-PD-1 antibody), for development and commercialization outside of Greater China.

About GEMSTONE-301 study

GEMSTONE-301 study (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 profile.

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.

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 GEMSTONE-302 study

GEMSTONE-302 (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 combined with chemotherapy as the first-line treatment in naïve patients with stage IV NSCLC vs. placebo combined with chemotherapy. The primary endpoint of the study was investigator-assessed PFS. Secondary endpoints included overall survival, BICR-assessed PFS and safety.

In August 2020, the GEMSTONE-302 study met its primary endpoint of significantly prolonging PFS and reducing the risk of disease progression or death by 50% with sugemalimab combined with chemotherapy compared to placebo combined with chemotherapy, as assessed by independent Data Monitoring Committee (iDMC) at the planned interim analysis. Specific study data were presented in a Proffered Paper Oral Presentation (Late-Breaking Abstract) at the ESMO Asia 2020.

In November 2020, the NMPA of China accepted the NDA for sugemalimab combined with chemotherapy for the first-line treatment of advanced squamous and non-squamous non-small cell lung cancer patients.

In July 2021, the final analysis of PFS from the GEMSTONE-302 study showed that sugemalimab in combination with chemotherapy demonstrated further improvement in PFS and the risk of disease progression or death was reduced by 52%, together with a trend of overall survival benefits. The two-year survival rate was 47.1%. Data were presented in a Mini Oral Presentation (Late-Breaking Abstract) at the IASLC 2021 World Conference on Lung Cancer (WCLC).

About CStone

CStone Pharmaceuticals (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 three drug approvals in Greater China, including two in Mainland China 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.

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