CStone announces positive GAVRETO® (pralsetinib) registrational study data for first-line treatment of advanced RET fusion-positive non-small cell lung cancer and plans to submit a new indication appl

CStone Pharmaceuticals, a leading biopharmaceutical company focused on researching, developing, and commercializing innovative immuno-oncology therapies and precision medicines, today announced data from the China registrational study of the global pivotal Phase 1/2 ARROW trial. The results demonstrated deep and durable clinical activity of GAVRETO® (pralsetinib) for the first-line treatment of Chinese patients with advanced RET fusion-positive non-small cell lung cancer (NSCLC), which is consistent with the global population. The overall safety is manageable, no new safety signal detected. GAVRETO is a potent and selective RET inhibitor discovered by CStone's partner Blueprint Medicines.

"Platinum-based chemotherapy is recommended as the standard first-line treatment for patients with RET fusion-positive NSCLC in China, but there is a need for new treatment options," said Professor Yi-long Wu of Guangdong Provincial People's Hospital, and Principal Investigator on the ARROW study China cohort, "The initial approval of GAVRETO in China heralds a new era for RET inhibitors in the treatment of RET fusion-positive NSCLC after platinum-based chemotherapy. With the promising data shown in the registrational study where GAVRETO is studied as a potential first-line treatment for Chinese patients with RET fusion-positive NSCLC, we very much look forward to the potential approval of broader indications in China."

"We are glad to see that the registrational study of GAVRETO for the first-line treatment of RET fusion-positive NSCLC patients in China has shown promising efficacy results and safety is manageable, adding more clinical evidence for GAVRETO," said Dr. Jason Yang, Chief Medical Officer of CStone. "We would like to thank all the investigators, patients and their families involved in this clinical study. We will initiate regulatory discussions with the China NMPA and look forward to potentially benefiting more patients soon."

CStone plans to submit new indication application to the China NMPA for GAVRETO as a first-line treatment for patients with RET fusion-positive NSCLC soon. Detailed study data will be presented at a future international academic conference.

In March 2021, GAVRETO was granted as one of new care medical supplies approval by the China NMPA as China's first selective RET inhibitor for the treatment of adult patients with locally advanced or metastatic RET fusion-positive NSCLC after platinum-based chemotherapy. The first batch of prescriptions was issued across multiple cities in China this month, benefiting Chinese patients. Additionally, in the recently published "2021 Clinical Guidelines for Molecular Pathological Detection of Non-small Cell Lung Cancer," RET testing was granted a recommendation for the detection of RET fusion-positive NSCLC patients. GAVRETO was included in the 2021 Chinese Medical Association guidelines for clinical diagnosis and treatment of lung cancer as the only recommended second-line or later therapy for RET fusion-positive stage IV non-squamous NSCLC that has progressed following platinum-based chemotherapy. In April 2021, the China NMPA accepted the supplemental new drug application of GAVRETO with priority review designation for the treatment of patients with advanced or metastatic RET-altered thyroid cancers. Following a regulatory review by the NMPA of China, the labeled indications for GAVRETO in China may be expanded to include advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy, and advanced or metastatic RET fusion-positive thyroid cancers who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate), if approved.

CStone has an exclusive collaboration and license agreement with Blueprint Medicines for the development and commercialization of GAVRETO in Greater China, which encompasses Mainland China, Hong Kong, S.A.R., China, Macau, S.A.R., China, and Taiwan, China.

About the ARROW Study

The ARROW study is a global phase I/II clinical study designed to evaluate the safety, tolerability and efficacy of GAVRETO in patients with RET fusion-positive NSCLC, RET-mutant medullary thyroid cancer (MTC) and other advanced solid tumors with RET fusions.

Data from the ARROW study were presented at the IASLC 2020 World Conference on Lung Cancer (WCLC). As a of a data cutoff date of May 22, 2020, the results showed that GAVRETO had robust and durable anti-tumor activity in Chinese patients with advanced or metastatic RET fusion-positive NSCLC after platinum-based chemotherapy. In 32 patients who had measurable disease at baseline, the confirmed overall response rate (ORR) was 56%, the median duration of response (DOR) was not reached, and the six-month DOR rate was 83%. GAVRETO was well-tolerated, and there were no adverse events related to treatment with GAVRETO that led to treatment discontinuation or death.

About RET fusion-positive 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.

In lung cancer, there are a number of somatic mutations, including EGFR, ALK, and ROS1, that can be targeted with approved therapies. RET fusions account for 1-2% of NSCLC patients, the majority of whom are non-smokers.

About GAVRETO (pralsetinib)

GAVRETO (pralsetinib) is a once-daily oral targeted therapy approved by the NMPA of China for the treatment of adults with locally advanced or metastatic rearranged during transfection (RET) fusion-positive NSCLC after platinum-based chemotherapy.

GAVRETO is approved by the U.S. Food and Drug Administration (FDA) for the treatment of three indications: adult patients with metastatic RET fusion-positive NSCLC as detected by an FDA approved test, adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC), and adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). These indications are approved under accelerated approval based on ORR and DOR. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

GAVRETO is not approved for the treatment of any other indication in China by the NMPA or in the U.S. by the FDA, or for any indication in any other jurisdiction by any other health authority.

GAVRETO is designed to selectively and potently target oncogenic RET alterations, including secondary RET mutations predicted to drive resistance to treatment. In preclinical studies, GAVRETO inhibited RET at lower concentrations than other pharmacologically relevant kinases, including VEGFR2, FGFR2, and JAK2.

Blueprint Medicines and Roche are co-developing GAVRETO globally (excluding Greater China) for the treatment of patients with RET-altered NSCLC, thyroid cancer, and other solid tumors. Blueprint Medicines and Genentech, a member of the Roche Group, are co-commercializing GAVRETO in the U.S., and Roche has exclusive commercialization rights for GAVRETO outside of the U.S. (excluding greater China). The European Medicines Agency validated a marketing authorization application for GAVRETO for the treatment of RET fusion-positive NSCLC, and the review is ongoing. The FDA granted breakthrough therapy designation to GAVRETO for the treatment of RET fusion-positive NSCLC that has progressed following platinum-based chemotherapy and for RET mutation-positive MTC that requires systemic treatment and for which there are no alternative treatments.

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, China. CStone's vision is to become globally recognized as a world-renowned biopharmaceutical company by bringing innovative oncology therapies to cancer patients worldwide.