Pralsetinib Approved for RET Fusion+ Metastatic NSCLC in Hong Kong, China

Pralsetinib (Gavreto) has been approved in Hong Kong, China, for use in treatment-naïve and pretreated adult patients with RET fusion–positive, metastatic non–small cell lung cancer (NSCLC), according to an announcement from CStone Pharmaceuticals.¹

The regulatory decision was supported by findings from the phase 1/2 ARROW study (NCT03037385), in which the agent elicited an overall response rate (ORR) of 79% (95% CI, 68%-88%) in treatment-naïve patients (n = 68), which comprised a complete response (CR) rate of 6%, and a partial response (PR) rate of 74%. In this group, the median duration of response (DOR) with pralsetinib was not yet reached (NR; 95% CI, 9.0-NR). Notably, 10% of patients experienced complete regression of their target tumors.

In the subset of patients who received prior platinum-based chemotherapy (n = 126), pralsetinib induced an ORR of 62% (95% CI, 53%-70%), which included a CR rate of 4%, and a PR rate of 58%; 12% of patients experienced complete regression of their target tumors. In this group of patients, the median DOR was 22.3 months (95% CI, 15.1-NR).

“We are very glad about the new drug application [NDA] approval of [pralsetinib] in Hong Kong, China, which came only 4 months after its NDA acceptance,” Frank Jiang, chief executive officer of CStone Pharmaceuticals, stated in a press release. “This came on the heels of the NDA approval of our first-in-class precision therapy avapritinib [Ayvakit] in this city. [Pralsetinib] has already been approved in Mainland China, and we are very excited to bring forward this innovative therapy to more patients in the Greater China region.”

ARROW enrolled patients with an advanced or metastatic solid tumor harboring a RET alteration per local assessment.² Patients were required to be at least 18 years of age, have measurable disease per RECIST v1.1 criteria, and an ECOG performance status of 0 or 1.

In the phase 2 dose-expansion portion of the trial, participants received pralsetinib at a daily dose of 400 mg. The primary end points of the trial were ORR per blinded independent central review and RECIST v1.1 criteria, as well as safety. Key secondary end points comprised DOR, clinical benefit rate (CBR), disease control rate (DCR), progression-free survival (PFS), and overall survival.

At a data cutoff date of November 6, 2020, a total of 471 patients comprised the safety population; these patients received the recommended phase 2 dose of the agent, which was 400 mg daily. Of these patients, 233 had RET fusion–positive NSCLC and 238 had RET-altered solid tumors. Of those with NSCLC, 216 patients comprised the measurable disease population; 115 discontinued treatment, the most common reason being due to disease progression (n = 70).

In the total population of patients with RET fusion–positive NSCLC (n = 216), the median age was 60 years (range, 26-87), 48% were male, 52% were White, 62% were never smokers, 63% had an ECOG performance status of 1, and 38% had brain metastases. Regarding prior treatment, 58% previously received platinum-based therapy, 19% received a prior multikinase inhibitor, and 31% received a prior PD-1/PD-L1 inhibitor.

Additional data from the trial presented during the 2021 ASCO Annual Meeting showed that in the treatment-naïve patients (n = 68), the DCR with pralsetinib was 93% (95% CI, 84%-98%), the CBR was 79% (95% CI, 64%-90%), and the median PFS was 13.0 months (95% CI, 9.1-NR; n = 75).

In the subset of patients who previously received platinum chemotherapy (n = 126), the DCR was 91% (95% CI, 95%-96%) with pralsetinib, the CBR was 74% (95% CI, 65%-81%), and the median PFS was 16.5 months (95% CI, 10.5-24.1; n = 136).

Regarding safety, 6% of the 471 patients in the overall safety population discontinued treatment with pralsetinib because of treatment-related adverse effects (TRAEs). In the subset of patients with RET fusion–positive NSCLC, the most common TRAEs included neutropenia (any grade, 42%; grade ≥3, 20%), aspartate aminotransferase increase (all grade, 39%; grade ≥3, 3%), anemia (any grade, 38%; grade ≥3, 13%), white blood cell count decrease (any grade, 30%; grade ≥3, 7%), alanine aminotransferase increase (any grade, 27%; grade ≥3, 3%), hypertension (any grade, 25%; grade ≥3, 12%), asthenia (any grade, 25%; grade ≥3, 2%), constipation (any grade, 24%; grade ≥3, 1%), and lymphopenia (any grade, 16%; grade ≥3, 9%), among others.

Treatment-related neutropenia resulted in treatment interruption in 15% of patients, and dose reduction in 14% of patients. Only 2 patients discontinued pralsetinib because of this toxicity.

References

1. CStone announces the NDA approval of GAVRETO (pralsetinib) for the treatment of RET fusion-positive treatment-naïve (first-line) and pretreated non-small cell lung cancer (NSCLC) in Hong Kong, China. News release. CStone Pharmaceuticals. July 15, 2022. Accessed July 18, 2022. https://bit.ly/3RISatS
2. Curigliano G, Gainor JF, Griesinger F, et al. Safety and efficacy of pralsetinib in patients with advanced RET fusion–positive non-small cell lung cancer: update from the ARROW trial. J Clin Oncol. 2021;39(suppl 15):9089. doi:10.1200/JCO.2021.39.15_suppl.9089