Suzhou, China, January 17, 2023— CStone Pharmaceuticals (“CStone”, HKEX: 2616), a leading biopharmaceutical company focused on research, development, and commercialization of innovative immuno-oncology therapies and precision medicines, announced today that the new drug application (NDA) for GAVRETO® (pralsetinib) has been approved in Taiwan, China for the treatment of adult patients with locally advanced or metastatic RET fusion-positive non-small cell lung cancer (NSCLC), advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy, and advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).
GAVRETO is a potent and selective RET inhibitor discovered by CStone’s partner Blueprint Medicines. 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, Macau, and Taiwan.
Dr. Jason Yang, Chief Executive Officer of CStone, said, “We are very glad about the NDA approval of GAVRETO in Taiwan, China, which came on the heels of the approval of AYVAKIT® (avapritinib) for the treatment of patients with advanced gastrointestinal stromal tumor harboring a PDGFRA D842V mutation in this market. GAVRETO has already been approved in several regions in Greater China, with robust and durable anti-tumor activity and a well-tolerated safety profile. With this NDA approval, we will provide a new treatment option for patients with RET-altered lung cancer and thyroid cancer in Taiwan, China. CStone is committed to delivering innovative medicines to address unmet medical needs for cancer patients. Moving forward, we will continue our efforts to accelerate the development of oncology therapies and to bring more high-quality drugs to patients worldwide.”
The NDA approval of GAVRETO in Taiwan, China is based on the results from the global phase 1/2 ARROW study. This trial is designed to evaluate the safety, tolerability, and efficacy of GAVRETO in patients with RET-fusion-positive NSCLC, RET-altered thyroid cancer, and other advanced solid tumors with RET fusions.
In September 2022, updated results from the global ARROW study were presented at the European Society for Medical Oncology (ESMO) Congress. In patients who had measurable disease at baseline, tumor response was assessed by blinded independent central review (BICR) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and all responses were confirmed. The results were reported as of a data cutoff date of March 4, 2022 in patients with RET fusion-positive NSCLC, and October 18, 2021 in patients with RET-altered thyroid cancer.
GAVRETO showed sustained clinical benefits in patients who received a starting GAVRETO dose of 400 mg once daily. In 260 patients with RET fusion-positive NSCLC across lines of therapy, the overall response rate (ORR) was 70.0%, and the median duration of response (DOR) was 19.1 months (95% CI: 14.5 months, 27.9 months). The most common treatment-related adverse events (TRAEs) in RET fusion-positive NSCLC patients were AST increased (44.5%), anaemia (42.3%), ALT increased (32.7%), neutrophil count decreased (31.0%), constipation (27.0%), hypertension (26.7%), white blood cell count decreased (26.3%), and neutropenia (21.4%).
In 62 treatment-naïve patients with RET-mutant MTC, the ORR was 77.4%, and the median DOR has not yet been reached (95% CI: not evaluable, not evaluable); in 61 patients with RET-mutant MTC who previously received cabozantinib or vandetanib, the ORR was 55.7%, and the median DOR was 25.8 months (95% CI: 18.0 months, not evaluable). In 22 patients with RET fusion-positive thyroid cancer who received prior systemic treatment, the ORR was 90.9%, and the median DOR was 23.6 months (95% CI: 15.1 months, not evaluable). In the RET-altered thyroid cancer safety population, 29 patients (16.6%) experienced serious treatment-related adverse events. TRAEs led to discontinuation in 5.7% of patients.
The updated data showed that GAVRETO had potent and durable anti-tumor activity in patients with advanced RET fusion-positive NSCLC, RET-mutant MTC and RET fusion-positive thyroid cancer, and the overall safety was generally manageable, with no new safety signals detected.
In August 2022, results from the ARROW study published in the biomedical journal Nature Medicinefurther supported GAVRETO’s durable anti-tumor activity (57% ORR, DOR 11.7 months 95% CI: 5.5, 19.0) and a generally well-tolerated safety profile in patients with other RET fusion-positive solid tumors, including pancreatic cancer and cholangiocarcinoma. The most common TRAEs were increased aspartate transaminase (38%), increased alanine transaminase (34%) and neutropenia (34%).
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 820,000 new lung cancer cases and 710,000 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 RET-altered Thyroid Cancer
Thyroid cancer is the most common endocrine malignancy with significantly increased incidence in recent years. According to the latest estimates on the global burden of cancer released by IARC, in 2020, there were about 220,000 new cases of thyroid cancer and the number of new cases in females reached about 170,000 in China. The incidence of thyroid cancer ranked 4th among all malignant tumors in females in urban areas.
Thyroid cancer is clinically divided into multiple subtypes, including medullary, differentiated (e.g., papillary, follicular, poorly differentiated, Hürthle cell), and anaplastic. The treatment and prognosis of different types of thyroid cancer vary according to the characteristics of the tumor.
RET fusions and mutations are key disease drivers in many cancer types, including NSCLC and several types of thyroid cancer. Approximately 10-20% of patients with papillary thyroid cancer (the most common type of thyroid cancer) carry RET fusions, and approximately 90% of patients with MTC (approximately 2-5% of thyroid cancers) carry RET mutations.
About GAVRETO (pralsetinib)
GAVRETO is a once-daily oral targeted therapy approved by the NMPA of China for the treatment of adults with locally advanced or metastatic RET fusion-positive NSCLC after platinum-based chemotherapy, and for the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant MTC who require systemic therapy, 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 treatment is appropriate). GAVRETO has been approved in Hong Kong, China for the treatment of adult patients with RET fusion-positive metastatic NSCLC, and in Taiwan, China for the treatment of adult patients with locally advanced or metastatic RET fusion-positive NSCLC, advanced or metastatic RET-mutant MTC who require systemic therapy, and advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).
GAVRETO is approved by the U.S. Food and Drug Administration (FDA) for the treatment of three indications: (i) adult patients with metastatic RET fusion-positive NSCLC as detected by an FDA approved test, (ii) adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant MTC, and (iii) 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). GAVRETO’s approval for these indications is based on ORR and duration of response (DOR). Additional approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.
The European Commission (EC) has granted conditional marketing authorization for GAVRETO as a monotherapy for the treatment of adult patients with RET fusion-positive advanced NSCLC not previously treated with a RET inhibitor. GAVRETO is not approved for the treatment of any other indication in Greater China, the U.S. or Europe.
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 United States, and Roche has exclusive commercialization rights for GAVRETO outside of the United States (excluding Greater China).
CStone (HKEX: 2616) is a biopharmaceutical company focused on research, development, and commercialization of 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 ten NDA approvals for its four drugs. Multiple late-stage drug candidates are now under pivotal clinical trials or registration. 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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1. Subbiah et al Nature Medicine;28: 1640-45 ↑
2. https://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf ↑