CStone Pharmaceuticals announced that the Taiwan Food and Drug Administration (TFDA) has confirmed the acceptance of the new drug application (NDA) for pralsetinib for the treatment of rearranged during transfection (RET) fusion-positive locally advanced or metastatic non-small cell lung cancer (NSCLC), advanced or metastatic RET-mutant medullary thyroid cancer (MTC), and advanced or metastatic RET fusion-positive thyroid cancer (TC) who are radioactive iodine-refractory (if radioactive iodine treatment is appropriate). Discovered by CStone's partner Blueprint Medicines, pralsetinib is a potent and selective RET inhibitor. CStone has an exclusive collaboration and license agreement with Blueprint Medicines for the development and commercialization of pralsetinib in Greater China, which encompasses Mainland China, Hong Kong, Macau and Taiwan.

The NDA acceptance of pralsetinib in Taiwan, China is based on the global phase 1/2 ARROW study, which is designed to evaluate the safety, tolerability and efficacy of pralsetinib in patients with RET fusion-positive NSCLC, RET-mutant MTC and other advanced solid tumors with RET fusions. Results from the ARROW trial in global patients with RET fusion-positive NSCLC were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting in June 2021. As of a date cutoff date of November 6, 2020, pralsetinib showed durable clinical benefits in patients with RET fusion-positive NSCLC who had measurable disease at baseline and received a starting dose of 400 mg once daily.

In 68 treatment-naïve patients, the overall response rate (ORR) was 79% (95% CI: 68%, 88%). The complete response (CR) rate was 6%, 10% of patients had complete regression of target tumors, and 74% of patients had a partial response (PR). The median duration of response (DOR) was not reached (95% CI: 9.0 months, not reached).

In 126 patients who previously received platinum-based chemotherapy, the ORR was 62% (95% CI: 53%, 70%). The CR rate was 4%, 12% of patients had complete regression of target tumors, and 58% of patients had a PR. The median DOR was 22.3 months (95% CI: 15.1 months, not reached).

As of the data cutoff date, a total of 471 patients were enrolled across tumor types with a pralsetinib dose starting at 400 mg once daily. The most common treatment-related adverse events (AEs) reported by investigators were neutropenia, increased aspartate aminotransferase, anemia, decreased white blood cell count, increased alanine aminotransferase, hypertension, constipation and asthenia. Results from the ARROW trial in global patients with RET-altered thyroid cancer were published in The Lancet Diabetes and Endocrinology in August 2021.

As of a data cutoff date of May 22, 2020, pralsetinib showed durable anti-tumor activity in patients with RET-altered thyroid cancer who received a starting dose of 400 mg once daily. In 55 patients with RET-mutant MTC previously treated with cabozantinib or vandetanib, the ORR was 60% (95% CI: 46%, 73%), and the median DOR was not reached (95% CI: 15.1 months, not estimable). In 21 systemic treatment-naïve patients with RET-mutant MTC, the ORR was 71% (95% CI: 48%, 89%), and the median DOR was not reached (95% CI: not estimable, not estimable).

In addition, the ORR was 89% (95% CI: 52%, 100%) in nine patients with RET fusion-positive thyroid cancer, and the median DOR was not reached (95% CI: not estimable, not estimable). In 142 patients with RET-altered thyroid cancer, the most common AEs were anemia, musculoskeletal pain, constipation, increased aspartate aminotransferase and hypertension.